Curriculum Vitae: MARY LARSEN BOUXSEIN
CURRICULUM VITAE
Name: MARY LARSEN BOUXSEIN
Office Address: Center for Advanced Orthopaedic Studies
Beth Israel Deaconess Medical Center, RN115
330 Brookline Avenue, Boston, MA 02215
Work phone: (617) 667-4594
Work email: mbouxsei@bidmc.harvard.edu
Work fax: (617) 667-7175
Education:
1987 B.S. General Engineering University of Illinois, Champaign, IL
1987 B.A. Economics
1989 M.S. Mechanical Engineering Stanford University, Stanford, CA
1992 Ph.D. Mechanical Engineering Stanford University, Stanford, CA
(Dennis R. Carter, PhD)
Postdoctoral Training:
1992-95 Postdoctoral Fellow Orthopedic Biomechanics Beth Israel Hospital
(PI: Wilson C. Hayes, PhD) Harvard Medical School
Faculty Academic Appointments:
1995-00 Instructor Department of Orthopedic Surgery Harvard Medical School, Boston
2001- Assistant Professor Department of Orthopedic Surgery Harvard Medical School, Boston
2006- Adjunct Assistant Professor Department of Mechanical Engineering Boston University
2008- Faculty Member MIT-HST Bioastronautics Program Massachusetts Institute of Technology
Hospital or Affiliated Institution Appointments:
1992- Senior Research Associate Department of Orthopedic Surgery Beth Israel Deaconess Medical Center
2010- Associate Biologist Department of Medicine Massachusetts General Hospital
Other Professional Positions:
1995-96 Consultant Bone densitometry / ultrasound Hologic, Inc, Waltham, MA
1997-99 Staff Scientist Bone Biology & Applications Genetics Institute, Cambridge, MA
2000-02 Principal Scientist Musculoskeletal Sciences Wyeth Research, Cambridge, MA
2001- Visiting Scientist Bone Biology & Genetics The Jackson Laboratory, Bar Harbor, ME
2006 - Consultant Preclinical and Clinical (Bone) Acceleron Pharma, Cambridge, MA
2008 Consultant Musculoskeletal Imaging Advisory Brd Merck & Co.
2010
Major Administrative Leadership Positions:
Local
2002-04 Co-Director Orthopedic Biomechanics Laboratory Beth Israel Deaconess Medical Center
2010- Co-Director Musculoskeletal Pathophysiology Course Harvard Medical School & MIT
(HST-020)
Committee Service:
National
2001-03 Steering Committee World Orthopedics & Osteoporosis Org
2001-03 Member
2004-05 Steering Committee, Bone Quality Meeting NIH & American Society for Bone and
Mineral Research
2004-05 Member
2005-06 Steering Committee, Bone Quality Initiative Meeting NIH
2005-06 Member
2008-09 Task Force on Standardization of Bone Structure NIH
Nomenclature
2008-09 Co-chair
2009 Standing Review Panel, Human Research Program NASA
2009 Member, Bone and Muscle Group
2010 - MD Curriculum Committee MIT – Harvard HST program
2010 - Member
International
2010 – 11 Scientific Program Committee European Calcified Tissue Society Member
Professional Societies:
1995- American Society of Biomechanics
1995 – present Member
1989-95 American College of Sports Medicine
1989-95 Member
1992- American Society for Bone & Mineral Research
1992 – present Member
1996 – 2001 Co-chair, Working group on Quantitative Ultrasound
2000 - 2003 Committee member, Membership Development Committee
2001 – present Member, Abstract selection committee
2007 – 2010 Member, Advocacy Committee
2009 – present Category chairperson (Bone biomechanics and quality) for abstract selection
2009 – 2010 Chair, Working Group on µCT Guidelines
1998- International Bone and Mineral Society
1998 – present Member
2007 – present Board member
2009 – 2010 Member, Scientific Advisory Committee for Davos Meeting
2010 – present Member, Nominations Committee
1999- Orthopedic Research Society
1999 – present Member
2009 – 2010 Member, Nominating Committee
2000- National Osteoporosis Foundation
2000 – present Member
2006 – present Member, Scientific Advisory Committee
2008 – present Program Committee for bi-annual meeting
2003- International Osteoporosis Foundation
2003 -- present Member
2003 – present Committee of Scientific Advisors
2004 – present Member, abstract selection committee for World Congress
2003 -- 06 Co-Chair, Working Group on Osteoporotic Fractures
2006 – 07 Co-Chair, Orthopedic Surgeons Initiative
2007 – present Co-Chair, Working Group on Bone Imaging / Bone Quality
Grant Review Activities:
1996- Osteoporosis Initiative US Dept of Defense
Study section member
2000 Children’s Skeletal Health Initiative Study Section NIH / NIDDK
Member and reviewer
2001 Skeletal Biology Development and Disease Study Section NIH / NIAMS
2001 Ad-hoc member
2003 Ad-hoc member
2006-09 Scientific & Clinical Grant Review Committee National Osteoporosis Foundation
2006-09 Member
2009 Skeletal Biology Development and Disease Study Section NIH / NIAMS
Reviewer, Challenge Grants
Editorial Activities:
Ad hoc Reviewer
New England Journal of Medicine
Journal of Bone and Mineral Research
Bone
Calcified Tissue International
Journal of Orthopaedic Research
Osteoporosis International
Journal of Biomechanical Engineering
American Journal of Medicine
Endocrinology
Journal of Clinical Densitometry
Journal of Biomechanics
Journal of Clinical Endocrinology and Metabolism
Other Editorial Roles
1996- Editorial Advisory Board Osteoporosis Management Today
1998-00 Editorial Board Member Calcified Tissue International
1998-01 Editorial Advisory Board Journal of Clinical Densitometry
2002-04 Deputy Editor Journal of Clinical Densitometry
2003 Co-Editor, Supplement on Bone Quality Osteoporosis International
2005- Editorial Board Member Osteoporosis International
2007- Editorial Board Member Bone
2007- Editorial Board Member BoneKey
2009- Editorial Board Member Therapeutic Advances in Musculoskeletal Disease
2010- Editorial Board Member Journal of Bone and Mineral Research
Honors and Prizes:
1987 Phi Beta Kappa Honor Society University of Illinois at Urbana-Champaign
1987 Student Leadership Award University of Illinois at Urbana-Champaign
1987 University Honors Bronze Tablet University of Illinois at Urbana-Champaign
Academic achievement, rank in top 3% of students
in graduating class
1993-95 National Research Service Award National Institutes of Health
(Post-doctoral fellowship) “Calcaneal ultrasound and fracture risk prediction”
1994 McCue Young Investigator Award Bath Ultrasound Symposium, Bath, England
1995 Young Investigator Award American Society for Bone and Mineral Research
1998 Best Ultrasound-Related Abstract American Society for Bone and Mineral Research Mtg
(PHF Nicholson & ML Bouxsein)
1999 Best Ultrasound-Related Abstract American Society for Bone and Mineral Research Mtg
(PHF Nicholson & ML Bouxsein)
2002 Young Investigator Fellowship American Federation on Aging Research
2005 Fuller Albright Award American Society for Bone and Mineral Research
*one award given annually to investigator under 40 yrs of age
for scientific achievement
Report of Funded and Unfunded Projects
Past Funding for Research Projects
1995-97 Prediction of vertebral fractures from spine radiographs: the Framingham Osteoporosis study
Charles A. King Trust / Postdoctoral Research Fellowship
PI ($50,000)
The goal of this study was to use biomechanical testing of human cadaveric spine segments to identify radiographic features associated with bone strength, and then test these features for their association with fracture in the Framingham cohort.
96. Using pQCT to predict forearm strength
Norland Medical Systems Inc. / Investigator initiated research project
PI
The objective of this study was to use cadaver testing to determine whether pQCT was associated with forearm strength.
97. Association between bone mineral density of the heel, assessed by SXA, and strength of the proximal femur
Dove Medical Systems Inc / Investigator initiated research project
PI
The objective of this study was to determine, using biomechanical testing of human cadaveric specimens to simulate a hip fracture, whether BMD of the heel was associated with femoral strength.
1995-96 Tibial ultrasound and bone strength
Myriad Ultrasound Inc. / Investigator initiated research project
PI ($35,800)
The objective of this study was to determine, using biomechanical testing of human cadaveric specimens to simulate a hip fracture, whether tibial ultrasound velocity was associated with femoral strength.
1995-96 Precision and correlation of alternative calcaneal bone assessment technologies in comparison with dual-energy x-ray absorptiometry (PI: S Greenspan)
Merck & Co, Inc / Investigator initiated research project
Co-investigator
The goal of this study was to compare reproducibility of five different heel ultrasound systems.
1995-96 Accuracy and precision testing of a new diagnostic technique in human cadaveric specimens
Merck & Co., Inc. / Investigator initiated research project
PI ($45,860)
The goal of this study was to determine accuracy and precision of single-xray absorptiometry of the finger using human cadaveric specimens.
1996-97 Accuracy and precision testing of the Schick single- and dual-energy techniques in human cadaveric specimens
Schick Technologies, Inc. / Investigator initiated research project
PI ($36,885)
The goal of this study was to determine accuracy and precision of single- and dual- X-ray absorptiometry of the finger using human cadaveric specimens, and compare these measurements to standard DXA-derived BMD.
97. Investigation of DXA in the presence of a metal prosthesis using the Hologic QDR-4500 fan beam system Hologic, Inc. / Investigator initiated research project
PI
The goal of this study was to use human cadaveric specimens to determine whether the presence of a metal implant influenced bone mineral density measurements.
01. Hip fracture risk prediction by QDR (PI: Wilson C. Hayes)
NIH / R01
Co-Principal Investigator
The goal of this study was to employ novel biomechanical approaches to improve the prediction of hip fracture risk.
02. Low cost methods for assessing osteoporotic fracture risk
NIH-NIAMS / 5R29AR044661 (FIRST award)
PI ($51,300)
The goal of this study was to explore the use of radiographs and ultrasound for prediction of bone strength in human cadaveric specimens, in order to develop new methods for predicting fracture risk in osteoporotic patients.
99. Use of Omnisense for predicting femoral strength
Sunlight Ultrasound Systems / Investigator initiated research project
PI
The objective of this study was to determine, using biomechanical testing of human cadaveric specimens to simulate a hip fracture, whether tibial ultrasound velocity was associated with femoral strength.
1999-00 Use of Omnisense for predicting forearm strength
Sunlight Ultrasound Systems / Investigator initiated research project
PI
The objective of this study was to determine, using biomechanical testing of human cadaveric specimens to simulate a wrist fracture, whether tibial ultrasound velocity was associated with femoral strength.
03. Role of ß-Arrestin2 in mediating the skeletal response to PTH
American Federation on Aging Research / Junior Faculty Career Award
PI ($50,000)
The goal of this study to investigate the role of ß-arrestin in mediating the skeletal and mineral metabolic response to intermittent PTH treatment.
04. Genetic analysis of vertebral strength (PI: CH Turner)
NIH – NIAMS / R01AR46530
PI on subcontract ($211,572)
The goal of this study was to use quantitative trait loci analysis to identify genetic determinants of vertebral microarchitecture and strength using inbred mice. Our role was to perform microCT imaging of mouse vertebrae to establish phenotype in ~ 1000 F2 mice.
06. Biology of IGF-1 in bone (PI: TC Clemens, University of Alabama, Birmingham, AL)
Veterans Affairs / Merit Review
Consultant
2001-06 Genetic and dynamic analysis of bone density (PI: WG Beamer, Jackson Laboratory, Bar Harbor, ME) NIH –NIAMS / 5R01AR043618
Consultant
The goal of this research is to use inbred mouse strains along with controlled breeding to identify quantitative trait loci that regulate bone mineral density (BMD).
06. Genetic epidemiology of osteoporosis (PI: X. Xu, University of Illinois at Chicago)
NIH- NIAMS / R01AR045651
PI on subcontract ($20,000)
This proposal aims to identify human genes responsible for osteoporosis and to enhance our understanding of the pathophysiology of osteoporosis by using peripheral DXA (pDXA) technology to measure proximal radial BMD in 15,000 sib pairs aged 40-64 years in an isolated population in Anqing, China. My role is to assist with protocol development for pDXA and assist with data interpretation.
05. Role of ß-Arrestin in mediating anabolic activity of PTH
NIH-NIAMS / R55AR049265
PI ($80,000)
The overall goal of this bridge funding was to improve our understanding of the mechanisms regulating the activity of PTH in bone by conducting complementary in vivo and in vitro experiments in mice deficient for beta-arrestin2 and in mice overexpressing beta-arrestin-2 in mature osteoblasts.
06. Healing of segmental defects in bone by gene transfer (PI: C Evans, Brigham and Women’s Hospital, Boston)
NIH / R01AR050243
PI on subcontract ($324,654)
The overall goal is determine efficacy of a gene transfer approach to deliver BMP-2 to critical sized segmental defects in a rat model. My role is to perform high-resolution µCT imaging and mechanical testing of the healing bony defects.
2004-07 QCT analysis of POWR trial
NPS Pharmaceuticals / Investigator initiated research project
PI, Member of Steering Committee
The overall goal of the study was to test the skeletal and mineral metabolic effects of PTH-once weekly. Our specific contribution was to analyze QCT scans of the hip and spine.
2005-08 Therapeutic Targeting of the Stem Cell Microenvironment (PI: D Scadden, Massachusetts General Hospital) NIH - NHLBI / U54 HL081030
PI on Subcontract ($111,216)
The goal of this program project grant is to determine whether PTH administration enhances efficacy of bone marrow stem cell transplants. My role is to perform microCT and biomechanical analyses on mouse bones, assist with data analysis, interpretation and writing.
07. Hormonal Control of Calcium Metabolism” (PI: J Potts, Massachusetts General Hospital, Boston, MA)
NIH-NIDDK / P01DK011794 ($195,210)
PI on subcontract; Director of Skeletal Phenotyping Core for Program Project Grant (
The program project grant is aimed at understanding the molecular, cellular and physiological actions of parathryroid hormone on bone and kidney and mineral ion homeostasis. The specific aims of the subcontract are to provide skeletal phenotyping data (microCT, mechanical strength testing) for normal and transgenic mice treated with PTH.
2005-09 Genetic Regulation of IGF-1 in Peak Bone Density in Mice (PI: CJ Rosen, Maine Medical Center Research Institute)
NIH-NIAMS / R01AR45433
Co-investigator, PI on Subcontract ($117,624)
The primary goals of this project are 1) to delineate the genes regulating serum IGF-1 by fine mapping of congenic mouse strains and studying effects on BMD and bone strength; 2) to study the role of IGF-binding proteins in modulating skeletal IGF-1; and 3) to determine the molecular mechanisms responsible for interstrain differences in skeletal IGF-1 expression. My contribution is to perform microCT and mechanical testing analyses on various mouse models.
08. Non-invasive Assessment of Femoral Strength
Merck & Company / Investigator initiated research project
PI ($240,804)
This main goal of this study is to evaluate the ability of different imaging modalities to predict the strength of human proximal femur in a sideways fall configuration. Secondary goals are to determine the relative contribution of BMD, femoral geometry, and cortical and trabecular bone microarchitecture to femoral strength.
2005-10 Epidemiology of Age-Related Fractures and Bone Loss” (PI: S Khosla, Mayo Clinic, Rochester, MN)Co-Inv NIH / R01AR027065
Co-Investigator, PI on subcontract ($25,000)
The goal of this study is to evaluate age- and sex-specific relationships among bone strength and loading in the context of osteoporotic fractures. My role is to assist with computation of bone strength indices and mechanical loading estimates.
2005-09 Role of ß-Arrestin in Mediating Anabolic Activity of PTH
NIH / R01AR049265
PI ($1,000,000)
The primary goals of this project are to 1) determine the role of ß-arrestin2 in mediating the in vivo skeletal response to PTH, 2) determine the role of ß-arrestin2 on the function of osteoblastic cells, and 3) determine whether specific rescue of ß-arr2 function in osteoblasts can restore the anabolic response to PTH in vivo.
Current Funding for Research Projects
2006-10 Low Frequency Vibration to Enhance Bone Mass in Elderly” (PI: D. Kiel, Hebrew Senior Life, Boston, MA)
NIH / R01AG025489
Co-Investigator, Member of Steering Committee, PI on subcontract ($195,213)
The goal of this multi-center trial is to evaluate the efficacy of low magnitude mechanical stimulation on bone density in elderly women and men. My role is to serve on the steering committee, perform analysis of QCT scans of the hip and spine, assist with data interpretation, and manuscript preparation.
2006-11 Mouse Models to Delineate a Unique Metabolic and Skeletal Network” (PI: C. Rosen, Maine Medical Center Research Institute)
NIH-NIAMS / R01AR054604
Co-Investigator, PI on subcontract ($140,000)
The objective of this study is to characterize the metabolic and skeletal effects of polymorphisms in two adjacent genes on mouse chromosome 6, namely Pparg and Alox5. My role is to perform micro-CT and mechanical testing analysis; and to assist with study design, data analysis, interpretation and writing.
12. Biomechanics of Vertebral Fractures: The Framingham QCT Cohort
NIH-NIAMS / 5R01AR053986
PI ($2,580,067)
The objective of this study is to assess the age-, sex- and vertebral-level specific structural determinants of vertebral fragility using QCT scans in participants from the Framingham study, and to conduct a case-control study of the factor-of-risk to predict vertebral fracture.
2007-12 Risk Factors for Age-Related Bone Loss (PI: D. Kiel, Hebrew Senior Life, Boston)
NIH-NIAMS / R01AR041398
Co-investigator, PI on subcontract ($251,041)
The objectives of this study are to use the Framingham Cohorts to: 1) examine association between lean mass and fracture; 2) measure vertebral trabecular volumetric bone density vTBMD from 3D-QCT scans; 3) determine heritability and perform genome-wide linkage and association studies for vTBMD; and 4) study association between key candidate genes and vTBMD. My role is to perform analysis of QCT scans for vTBMD, and assist with data analysis, interpretation and writing.
2007-12 Serum IGF-1 Delivery Systems and its Role in Determining Skeletal Integrity” (PI: S. Yakar, Columbia University, New York, NY)
NIH-NIAMS / R01AR054919
PI on subcontract ($154,236)
The objective of this study is to explore the role of serum IGF-1 and its delivery systems (binding proteins and acid labile subunit) on skeletal integrity through use of mouse models with targeted direction of key IGF delivery system components. My role is to perform microCT and mechanical testing of mouse bones, and assist with data analysis, interpretation and writing.
2008-13 Race/Ethnic Disparities in Fall Risk and Bone Strength Among Men (PI: A. Araujo, New England Research Institute)
NIH-NIA / R01AG020727
Consultant ($65,000)
The objective of this study is to explore risk factors for fractures among a population-based study of Caucasian, African American, Hispanic and Asian men. My role is to assist in developing protocol for measurement of bone microarchitecture by high-resolution peripheral quantitative computed tomography, compute estimates of bone strength and mechanical loading during falls and daily activities, and help with data interpretation and manuscript preparation.
2009-11 Musculoskeletal Response to Partial Weight Bearing
NIH-NIAMS / R21AR057522-01
PI ($275,000)
The objectives of this study are to characterize the mechanical environment and explore the musculoskeletal responses to a novel partial weight-bearing system for use in mice.
11. Effects of Perinatal Diet on Developmental Programming of the Skeleton
NIH-NIAMS / RC1 AR058389 (ARRA Challenge Grant)
PI ($550,313)
This project will determine whether, via developmental programming, maternal calorie restriction or high fat diet influences acquisition of bone mass, microarchitecture and strength in mice.
12. Maintenance of Skeletal Integrity in Spaceflight: Interaction among Partial Weight Bearing, Microgravity and Novel Therapeutics
NASA / NNX10AE39G
PI ($180,589)
The goal of this project is to use a mouse model to determine the efficacy of novel therapeutics (ie, antibody to RANK-ligand and antibody to sclerostin) in preventing skeletal deterioration due to partial weight bearing and full hindlimb suspension.
Current Unfunded Projects
2009- PI Use of microindentation to assess bone tissue quality
The goal of this study is to use a novel microindentation system to describe the variation in bone tissue properties according to age, sex, skeletal site, diet, and exposure to anabolic and anti-resorptive therapies.
Report of Local Teaching and Training
Teaching of Students in Courses
1998-2000 Functional Human Anatomy (HST 010; Med Sciences 250a,b) Harvard Medical School
1st year medical students (HST) and graduate students (HST) 15 3-hr lab/dissection sessions
Role: Instructor (Course director: Farish Jenkins) 3-5 1-hr lectures
4-6 1 hr pro-sections lectures
Exam preparation & grading
2008 Musculoskeletal Pathophysiology (HST020) Harvard Medical School
1st and 2nd year medical students (HST) and graduate students (HST) 2 1-hr lectures
Role: Invited lecturer (Course director: Dwight Robinson) Prepare and grade 1 homework
2009- Musculoskeletal Pathophysiology (HST020) Harvard Medical School
1st and 2nd year medical students (HST) and graduate students (HST) 3 1-hr lectures
Role: Invited lecturer Assisted with exam preparation
Assisted with syllabus and
hosting invited lecturers
2010-11 Musculoskeletal Pathophysiology (HST020) Harvard Medical School
1st and 2nd year medical students (HST) and graduate students (HST) Develop syllabus
Role: Co-Director of Course 4 1-hr lectures
Attend all lecture sessions
Prepare and grade exam
Formal Teaching of Residents, Clinical Fellows and Research Fellows
2009 Bone Biomechanics Massachusetts General Hosp
Endocrine Fellows and post-docs One hour lecture
2009 Advances in Skeletal Imaging Massachusetts General Hosp
Endocrine Fellows and post-docs One hour lecture
2010 Bone Biomechanics Massachusetts General Hosp
Endocrine Fellows and post-docs One hour lecture
2010 Advances in Skeletal Imaging Massachusetts General Hosp
Endocrine Fellows and post-docs One hour lecture
Laboratory and Other Research Supervisory and Training Responsibilities
Formally Supervised Trainees
Training Name PositionWhile Current Position
Duration Training
1992-93 Talya Toledano BS Candidate (HU) MD, Columbia University
1993-94 Kendrick Boardman BS Candidate (MIT) PhD, Northwestern University
1994-95 Stefan Radloff MS Candidate (MIT) Engineer, Intel Corporation
1995-96 Brian Coan BS Candidate (MIT) MD/MBA, Resident, Plastic Surgery, Duke Univ
1997-98 Soon Lee MD Candidate (Tufts) MD, Rehab. Medicine, Baltimore, MD
1997-99 Patrick Nicholson Post-doc Independent Investigator, London, UK
1999-00 Kristy Salisbury BS Candidate (BU) MD/PhD Candidate, Boston University
1999-01 Cynthia Luppen Res Assistant Post-doctoral Fellow, Stanford University
2000 Monique Muller PhD Candidate Assistant Professor McMaster University
2001 J.D. Johnston MS Candidate PhD Candidate, University of British Columbia
2001-02 Parikha Solanki BS Candidate (BU) Patent Facilitator, US Gov’t
2001-03 Deborah Sternlight MD Candidate (HMS) Resident in Dermatology, UCSF
2002-03 Kelly Myers BS Candidate (BU) MD Candidate, Mt. Sinai Medical School, NY
2002-04 Melissa Russ Research Asst MS, Wollongong University, Australia
2002-03 Jody McClean BS Candidate (BU) Research Assistant, Boston University
2003-04 Jessica Swenson BS Candidate (BU) BS, Boston University
2003-07 Erika Wagner PhD Candidate (MIT) Executive Director of Mars Gravity Project at MIT
Director of X-Prize MIT
2004-05 Danielle Abramson Post-doc Patent facilitator
2005-06 Lope Barrero Sc.D. Candidate (HSPH) Sc.D rec’d in 2007; Harvard School of Public Health
Currently researcher and consultant at the Center for Ergonomics Studies of School of Engineering of Javeriana University in Bogotá, Colombia.
2005-06 Laura Little B.S. Candidate (BC) MS Physical Therapy
2005-07 Eyal Rosen, DDS Research Fellow Residency Program in Dentistry, Israel
2005-06 David Karasik Instructor, HMS Associate Professor, Dept of Medicine, HMS
2006 Batya Feldman BS Candidate (MIT) BS, Mechanical Engineering, MIT
2006-07 Julienne Brouwers PhD Candidate received PhD, Eindhoven University
2006-07 Michal Ruchelsman BS Candidate (MIT) Rec’d BS, Accepted to medical school
2006-07 Christina Piron BS Candidate (BU) MD Candidate, Ohio University
2006-07 Andy Mach BS Candidate (BU) Working, Engineering Firm
2006-07 Neil Patel BS Candidate (BU) Working, Consulting Firm
2006-07 Erica Thrall MS Candidate (BU) Technical writer, the Mathworks
2007-08 Lisa Samelson Instructor Instructor, Dept of Medicine, HMS
2007-09 Rahel Eisenberg BS Candidate (MIT) Consultant
2008-09 Nishina Thomas BS Candidate (BU) MD Candidate, University of Texas San Antonio
2007- Maureen Devlin, PhD Post-doctoral fellow current T32, F32 recipient
2008- Blaine Christiansen, PhD Post-doctoral fellow Assistant Professor, Dept of Orthopedic Surgery
University of California, Davis
2008- Sravisht Iyer MD Candidate (HST)
2008- Rachel Ellman PhD Candidate (HST-MIT)
2008- Jordan Spatz PhD Candidate (HST-MIT)
2009 Yoo Mee Kim, MD,PhD Research fellow
2009- Benjamin Roberts MS Candidate (BU)
2009- Alex Bruno PhD Candidate (HST-MIT)
2010- Sean Serrell MS Candidate (BU)
2010- Marjtin deKooter MS Candidate, Visiting Fellow Eindhoven Technical University
The Netherlands
2010 Advhait Shaw BS Candidate (Tufts)
2010 Sneh Shah BS Candidate (BU)
2010 Sarah Sprague BS Candidate (MIT)
* Abbreviations: HMS = Harvard Medical School, BU = Boston University, MIT = Massachusetts Institute of Technology, HSPH = Harvard School of Public Health, BC = Boston College, HU = Harvard University
Formal Teaching of Peers (e.g., CME)
Local Invited Presentation (seminars, grand rounds)
2003 Mechanisms of Osteoporosis Therapies: A Biomechanical Perspective / Geriatrics Grand Rounds,
Beth Israel Deaconess Medical Center, Boston, MA
2003. Pins, Plates and Plaster are Not Enough/ Harvard Combined Orthopaedic Grand Rounds
Massachusetts General Hospital, Boston, MA
2004. Leptin and Bone: Is It Sympathetic / Endocrine Grand Rounds
Beth Israel Deaconess Medical Center, Boston, MA
Report of Regional, National and International Invited Teaching and Presentations
Regional
1995 Bone Density Changes in Human Athletes / Invited Speaker
Bone Remodeling Workshop, sponsored by Tufts University School of Veterinary Medicine, Concord, MA
1996 Etiology of Age-Related Fractures: a Biomechanics Perspective / Invited Speaker
Division of Human Performance and Nutrition, Tufts University Medical School, Boston, MA
1999 Age-Related Fractures: Etiology and Prevention / Invited Speaker, Seminar Series
The Jackson Laboratories, Bar Harbor, ME
2001 Genetics of Skeletal Fragility / Invited Speaker, Seminar Series
Forsyth Institute, Boston, MA
2001 Mechanisms of Anti-Resorptive Therapies / Plenary Speaker
New England Bone Club, Prouts Neck, ME.
2003 Role of ß-arrestin in skeletal homeostasis / Invited Speaker, Seminar Series
Forsyth Institute, Boston, MA
2003 Biomechanics of Fractures / Plenary Speaker
New England Regional Bone Symposium, Sugarloaf, ME
2003. Effects of Osteoporosis Agents on Bone Strength/ Endocrine Grand Rounds
Tufts Medical School, Boston, MA
2004. Beyond BMD: Understanding Bone Strength /Grand Rounds, Rehabilitation Medicine Program
New England Medical Center, Boston, MA
2005 Age-Related Fractures: Beyond BMD / Grand Rounds
Department of Physical Medicine and Rehabilitation, New England Medical Center, Boston, MA.
2007 Oversuppression of bone turnover: potential for too much of a good thing? / Plenary speaker
New England Bone Club, Portland, ME
National
1996 Etiology and Prevention of Age-Related Fractures / Plenary Speaker
American College of Sports Medicine Annual Meeting, Minneapolis, MN
1997 Assessment of Osteoporosis: What Has Technology Done for Us? / Invited Speaker
Medical Technologies for Women: Moving Towards the 21st Century. Office of Technology and Assessment. Washington, DC.
1996. Beyond Bone Density: Biomechanical Assessment of Fracture Risk / Plenary Speaker
International Society for Clinical Densitometry, San Diego, CA.
1996. Age-Related Fractures: Beyond BMD / Workshop of Musculoskeletal Aging
Stanford University & Geriatrics Research and Education Center, Palo Alto Veterans Administration Medical Center, Stanford, CA.
1997 Bone Failure: How Bone Responds to Stress, How it Fails Under Load and How these Events Relate to Normal Activities of Living / Part of CME Program titled “Back to the Future — Osteoporosis: Current Practice and Future Directions”
Inova Fairfax Hospital, Falls Church, VA
1997 Quantitative Ultrasound, Bone Quality and Bone Strength / Invited Symposium Speaker
Working Group on Quantitative Ultrasound, American Society for Bone and Mineral Research Annual Meeting, Cincinnati, OH.
1999 Bone Quality and Mechanical Performance in the Prevention of Fractures / Lecturer
The Endocrine Society Annual Meeting, San Diego, CA
1999 Biomechanics of Age-Related Fractures: Beyond BMD / Baltimore Bone Club
Baltimore, MD
1999 Acceleration of Fracture Healing with rhBMP-2 / Endocrine Grand Rounds
Oregon Health Sciences University, Portland, OR
1999 Biomechanics of Osteoporotic Fractures: Beyond BMD”, Plenary Speaker
National Consultant’s Meeting, Merck & Co., Phoenix, AZ (sponsored by Merck & Co.)
1999 Quantitative Ultrasound as a Surrogate Endpoint for Fracture Risk in Osteoporosis Studies / Plenary Speaker
NIH and FDA Conference on Biomarkers and Surrogate Endpoints, Bethesda, MD
1999 Bone Biology and the Etiology of Age-Related Fractures / Invited Speaker
Annual Meeting, Merck National Metabolic Bone Health Science Associates, Atlanta, GA (sponsored by Merck & Co.)
1999 Bone Quality and Mechanical Performance in the Prevention of Fractures / Invited Symposium Speaker The Endocrine Society Annual Meeting, San Diego, CA
1999 Use of Quantitative Ultrasound in Osteoporosis Diagnosis”, Invited Speaker, Seminar Series
Department of Health and Human Performance, Oregon State University, Corvallis, OR
2000 Biomechanics of Age-Related Fractures / Grand Rounds
Department of Endocrinology, Indiana University Medical School, Indianapolis, IN
2000 Vertebral Strength / Plenary Speaker
International Society of Clinical Densitometry Annual Meeting, Phoenix, AZ
2000 Etiology of Osteoporosis / Seminar Series
Sparks Regional Medical Center, Fort Smith, AR
2000 The Biomechanics of Osteoporotic Fractures: Beyond BMD / Plenary Speaker
Metabolic Bone Disease Society of Colorado Annual Meeting, Denver, CO.
2000 Biomechanics of Age-Related Fractures: New Insights into the Prevention and Treatment of Osteoporosis / Seminar Series
Foundation for Osteoporosis Research, Oakland, CA
2000 Bone Structure and Function / Invited Speaker
NIH Consensus Development Conference on Osteoporosis, Bethesda, MD
2000 Building Bone with Bone Morphogenetic Protein: Promise and Pitfalls”, Invited Speaker, Seminar Series
Department of Physiology, University of Arkansas Medical School, Little Rock, AR
2000 Understanding Age-Related Fractures: Etiology and Prevention / Grand Rounds
Department of Endocrinology, University of Arkansas Medical School, Little Rock, AR
2001 Biomechanics of Osteoporotic Fractures – Beyond BMD and into Bone Quality / Plenary Speaker International Society for Clinical Densitometry, Dallas, TX.
2001 Biomechanics of Osteoporotic Fractures – Beyond BMD / Plenary Speaker
Annual Seminar: Modern Approaches to Diagnosis and Treatment of Osteoporosis. University of Cincinnati, Cincinnati, OH
2001 Biomechanics of Osteoporotic Fractures and Therapies / Plenary speaker
Sante Fe Bone Symposium, Sante Fe, NM
2001 New Innovations in Assessing Skeletal Phenotypes in Humans / Plenary Speaker
Skeletal Genetics Mtg, NIH, Bethesda, MD.
2001 Role of Biomechanics in the Etiology of Age-Related Fractures / Invited Speaker
New York Metropolitan Bone Club, New York, NY
2001 How Do Anti-Resorptive Therapies Inhibit Fracture Risk: A Biomechanical Perspective / Invited Speaker
Metabolic Bone Disease National Consultants Meeting, Las Vegas, NV (sponsored by Proctor & Gamble)
2002 Understanding Osteoporosis: Risk Factors and Beyond / Plenary Speaker
Geriatric Medicine Update, University of Arkansas, Little Rock, AR.
2002 Etiology of Age-Related Fractures — Beyond BMD / Plenary Speaker
12th Annual Cleveland Review of Rheumatic Diseases, Cleveland Clinic, Cleveland, OH.
2002 Mechanism of Action of Osteoporosis Therapies: A Biomechanical Perspective / Plenary Speaker
12th Annual Cleveland Review of Rheumatic Diseases, Cleveland Clinic, Cleveland, OH
2002 Impact of Bone Remodeling on Bone Quality / Speaker
Ancillary Symposium, Endocrine Society Annual Meeting, San Francisco, CA.
2002 Bone quantity versus bone quality / Plenary Speaker
Bone & Basal, Insights for Endocrinologists, Santa Barbara, CA. (sponsored by the Alliance for Better Bone Health)
2002 Mechanisms of Osteoporosis Therapies / Grand Rounds
Department of Geriatrics, University of Pennsylvania, Philadelphia, PA
2002 Mechanisms of Osteoporosis Therapies: A Biomechanical Perspective / Invited Speaker
National Consultants Meeting, Miami, FL (sponsored by Merck & Co)
2002 BMP-2 for Treatment of Osteoporosis: Potential and Pitfalls / Speaker
Advances in Mineral Metabolism Annual Meeting, Snowmass, CO
2002 Genetics and Animal Models of Osteoporosis / Plenary Speaker
15th Annual Bone Densitometry Workshop, Monterey, CA
2002 Bone Microarchitecture / Meet the Professor Session
American Society for Bone and Mineral Research Annual Meeting, San Antonio, TX
2002 Mechanisms of Osteoporosis Therapies / Invited Speaker, Seminar Series
Department of Orthopaedics, University of Pittsburgh Medical School, Pittsburgh, PA
2002 Understanding Osteoporotic Fractures: Beyond BMD”, Invited Speaker
Rheumatology Seminar Series, Mercy Hospital, Pittsburgh, PA
2002 Genetics of Osteoporosis: Mouse to Man”, Invited Speaker, Seminar Series
Endocrine Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
2003 New Insights into Osteoporosis / Symposium Speaker
American College of Physicians Annual Mtg, San Diego, CA
2003 Mechanisms of Osteoporosis Therapies / Symposium Speaker
American Academy of Clinical Endocrinologists Annual Meeting, San Diego, CA.
2003 New Insights into Bone Quality / Symposium Speaker
Endocrine Society Annual Meeting, Philadelphia, PA. (sponsored by Eli Lilly & Co.)
2003 Aspects of Bone Quality / Internet Lecture Series (12 lectures in 1 year)
(Sponsored by Enable Healthcare)
2003 Clinical Perspectives on Bone Density, Bone Quality and Fracture Risk / Invited Speaker
NIH Symposium on Bone Quality, Bethesda, MD
2003 Biomechanics of Fractures: Beyond BMD / Invited Symposium Speaker
Mini-symposium, American Society for Bone and Mineral Research Annual Meeting, Minneapolis, MN
2004 Non-invasive assessment of skeletal strength / Invited Speaker
Sun Valley Hard Tissue Workshop, Sun Valley, ID
2004 Evaluating Age- and Sex-Related Changes in Bone Strength Using QCT / Invited Speaker
Metabolic Bone Diseases Interest Group, Oregon Health Sciences University, Portland, OR
2004 Effects of Osteoporosis Agents on Bone Quality / Grand Rounds
Department of Endocrinology, UCSF, San Francisco, CA
2004 Effects of Osteoporosis Agents on Bone Strength / Grand Rounds
Department of Endocrinology, Tufts Medical School, Boston, MA.
2004 The Impact of Bone Quality on Bone Strength / Symposium Speaker
American Society of Clinical Endocrinologists Annual Meeting, Boston, MA.
2004 Clinical Significance of Bone Quality / Symposium Speaker
American College of Obstetrics and Gynecology Annual Meeting, Philadelphia, PA
2004 Role of Bone Quality / Lecturer
1st Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA UCSF Osteoporosis Course, San Francisco, CA
2004 Effects of Osteoporosis Therapies on Bone Quality / Grand Rounds
Department of Endocrinology, Oregon Health Sciences University, Portland, Oregon.
2005 How Do Osteoporosis Drugs Effect Bone Strength? / Plenary Lecture
National Osteoporosis Foundation Annual Meeting, Washington, DC.
2005 Biomechanics of Age-Related Fractures / Faculty Lecturer
2nd Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA
2005 Bone Quality / Faculty Lecturer
2nd Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA.
2005 New Developments in the Non-Invasive Assessment of Bone Strength / Satellite Symposium Speaker ASBMR Annual Meeting, Nashville, TN (sponsored by the Alliance for Better Bone Health)
2005 Determinants of Bone Strength / Speaker
Therapeutic Advances in Medicine Televised Series, Milwaukee, MN
2005 Effect of Macroarchitecture on Bone Strength / Invited Speaker
Joint NIH- American Society for Bone and Mineral Research Meeting on Bone Quality, Bethesda, MD
2005 Non-Invasive Assessment of Bone Strength / Invited Speaker
Department of Radiology Research Seminar, UCSF Department of Radiology, San Francisco, CA
2005 Assessment of Bone Microarchitecture / Invited Plenary Speaker, State-of-the-Art Lecture
ASBMR Annual Meeting, Nashville, TN
2005 Update on NIH- American Society for Bone and Mineral Research Bone Quality Meeting / Invited Symposium Speaker
Bone Microarchitecture Working Group, American Society for Bone and Mineral Research Annual Meeting, Nashville, TN
2005 Use of Non-Clinical Data to Support Validation of Fracture Surrogates / Invited Speaker
NIH Consortium Meeting on Bone Quality, Bethesda, MD
2006 Biomechanics of Skeletal Fragility / Plenary Speaker
International Society of Clinical Densitometry Annual Meeting, San Diego, CA.
2006 Assessment of Microarchitecture using CT / Symposium Speaker
International Society of Clinical Densitometry Annual Meeting, San Diego, CA
2006 Use of Finite Element Analysis to Assess Bone Strength / Symposium Speaker
International Society of Clinical Densitometry Annual Meeting, San Diego, CA.
2006 Beyond BMD: Bone Quality, Bone Strength and How to Measure Them / Faculty Lecturer
3rd Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA.
2006 Bone Quality and Bone Strength / Invited Faculty
1st Annual Fellows’ Forum in Metabolic Bone Diseases, sponsored by the Endocrine Fellows Foundation and the American Society for Bone and Mineral Research, Philadelphia, PA.
2006 Bone Imaging: Quality Matters / Clinical Symposium Speaker
American College of Rheumatology Annual Meeting, Washington DC.
2006 Other Imaging Modalities: MicroCT / Invited Symposium Speaker
International Society for Clinical Densitometry Annual Meeting, San Diego, CA (sponsored by Merck & Co).
2006 Effect of Osteoporosis Therapies on Bone Strength / Grand Rounds
Department of Endocrinology, Northwestern University Medical Center, Chicago, IL
2006 Determinants of Bone Strength / Invited Symposium Speaker
American College of Sports Medicine Annual Meeting, Denver, CO
2007 Bone Quality / Meet the Professor Session
National Osteoporosis Foundation’s 7th International Symposium on Osteoporosis, Washington DC.
2007 Beyond BMD: Bone Quality, Bone Strength / Faculty Lecturer
4th Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA.
2007 Non-invasive Assessment of Bone: What’s New in 2007? / Faculty Lecturer
4th Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA.
2007 Bone Quality and Bone Strength / Faculty lecturer
2nd Annual Fellows’ Forum in Metabolic Bone Diseases, sponsored by the Endocrine Fellows Foundation and the American Society for Bone and Mineral Research, Honolulu, HI
2008 Beyond BMD: Bone quality and bone strength / Faculty Lecturer
5th Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA.
2008 Bone Quality and Bone Strength / Faculty Lecturer
3rd Annual Fellows’ Forum in Metabolic Bone Diseases, sponsored by the Endocrine Fellows Foundation and the American Society for Bone and Mineral Research, Montreal, Canada
2009 Why bones break / Keynote Speaker
Pediatric Bone Health Symposium, sponsored by the Pediatric Bone Health Consortium, University of California San Francisco, San Francisco, CA
2009 Epidemiology and Risk Factors for Osteoporosis / Faculty Lecturer
6th Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA.
2009 Beyond BMD: Bone Quality, Bone Strength / Faculty Lecturer
6th Annual Training Course: Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF, San Francisco, CA.
2009 Non-Invasive Assessment of Bone Microarchitecture / Meet the Professor Session
American Society for Bone and Mineral Research, Denver, CO
2009 Non-invasive Imaging for Assessment of Fracture Risk: The Promise of New Technologies to Improve Outcomes in Clinical Practice / Plenary Speaker
Metabolic Bone Disease Society of Colorado, Denver, CO
2009 Effect of diet on skeletal acquisition / Invited Speaker
Pediatric Bone Health Symposium, sponsored by the Pediatric Bone Health Consortium, University of California San Francisco, San Francisco, CA
International
1998 Quantitative Ultrasound and Bone Strength / Plenary Speaker
Workshop on Quantitative Ultrasound, Heidelberg, Germany, May.
2002 The Role of Bone Quality in the Pathophysiology of Osteoporosis / Plenary Speaker
29th European Symposium on Calcified Tissues, Zagreb, Croatia.
2002 Genetic Determinants of Vertebral Architecture and Strength / Invited Speaker
Seminar Series, Division of Bone Diseases, University Hospital, Geneva, Switzerland.
2003 The Role of ß-Adrenergic Signaling in Bone / Invited Speaker
Seminar Series, Division of Bone Diseases, University Hospital, Geneva, Switzerland.
2003 Mineralization Density and Distribution: Effects on Fracture Risk / Invited Speaker
Global Osteoporosis Advisory Board Meeting, Nice, France (sponsored by Eli Lilly & Co)
2003 Bone Quality and Skeletal Fragility / Plenary Speaker
International Bone and Mineral Society Annual Meeting, Osaka, Japan.
2003 Bone Quality: Myth or Meaningful / Grand Rounds
Department of Rheumatology, Hôpital Eduard Herriot, University of Lyon, Lyon, France
2003 Proving that Bone Quality Counts / Invited Speaker
4th European Conference on the Economic Aspects of Osteoporosis and Arthritis, Nice, France
2004 Understanding Bone Strength / Invited Symposium Speaker
Nuffield Orthopaedic Centre, Oxford University, Oxford, UK
2004 Bone Quality: From Basics to Clinics / Invited Speaker
5th International Symposium on Women’s Health and Menopause, Florence, Italy
2004 Understanding Bone Strength / Plenary Speaker
Annual Meeting of the Turkish National Osteoporosis Society, Istanbul, Turkey
2004 Effect of Anti-Resorptive Agents on Bone Strength / Invited Symposium Speaker
National Thought Leaders Meeting, Tokyo, Japan (sponsored by the Alliance for Better Bone Health)
2005 Bone Structure and Function / Faculty Lecturer
14th International Osteoporosis Foundation Advanced Training Course on Osteoporosis, Lyon, France
2005 Update on Skeletal Imaging / Faculty Lecturer
14th International Osteoporosis Foundation Advanced Training Course on Osteoporosis, Lyon, France
2005 Genetic Effects on Estrogen-Deficiency Induced Bone Loss”, Invited Speaker
Seminar Series, Division of Bone Diseases, University Hospital, Geneva, Switzerland
2005 Understanding Bone Strength / Invited Speaker
Actonel State Council Meeting, Sydney, Australia (sponsored by Proctor & Gamble)
2005 Clinical Relevance of Microarchitecture / Invited Speaker
Actonel State Council Meeting, Sydney, Australia (sponsored by Proctor & Gamble)
2005 Bone Quality / Plenary Speaker
Osteoporosis Outreach Program, St. Vincent’s Hospital, Toronto, Canada
2005 Does Size Matter? Sex-specific differences in bone size and strength / Invited Speaker
Osteoporosis in Men Conference, Genoa, Italy
2006 Bone Structure and Function / Faculty Lecturer
15th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France
2006 Biomechanics of Fractures / Faculty Lecturer
15th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France
2006 Update on Imaging Techniques / Faculty Lecturer
15th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France
2006 Non-Invasive Assessment of Bone Microarchitecture / Plenary Presentation
Annual Meeting of the German Osteology Society, Cologne, Germany
2006 Genetics of Bone Strength / Plenary Presenation
Annual Meeting of the German Osteology Society, Cologne, Germany
2006 Interaction between Bone Strength and Skeletal Loading / Plenary Presentation
World Congress on Osteoporosis, Toronto, Canada
2006 Clinical Importance of Bone Structural Analysis in Patients with Osteoporosis Treated with Bone Active Agents / Symposium Speaker
Annual Meeting of the European Rheumatology Society (EULAR), Amsterdam, The Netherlands.
2006 Non-Invasive Imaging of Microarchitecture with the XtremeCT / Symposium Speaker
Annual Meeting of the Australia/New Zealand Bone and Mineral Society, Port Douglas, Australia.
2006 Structural and Material Basis of Skeletal Fragility / PlenarySpeaker
Annual Meeting of the Australia/New Zealand Bone and Mineral Society, Port Douglas, Australia.
2007 Clinical assessment of bone architecture in 2007 / Plenary Speaker
Seventh European Congress on Clinical and Economic Aspects of Osteoporosis and Arthritis, Porto, Portugal
2007 Determinants of bone strength / Invited speaker
Satellite Symposium, European Calcified Tissue Society, Copenhagen, Denmark (sponsored by Roche)
2007 Assessment of bone strength / Plenary Presentation
United Kingdom National Osteoporosis Society, 12th Conference on Osteoporosis, Edinburgh, UK
2007 Oversuppression of bone turnover: potential for too much of a good thing / Grand Rounds
Department of Rheumatology, University Hospital, Zurich, Switzerland.
2007 Novel approaches for assessing bone strength and predicting fracture risk / Invited speaker
Seminar Series, Division of Bone Diseases, University Hospital, Geneva, Switzerland.
2008 Bone Structure and Function / Faculty Lecturer
16th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France
2008 Biomechanics of age-related fractures / Faculty Lecturer
16th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France
2008 New imaging techniques for assessing bone strength / Faculty Lecturer
16th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France
2008 Assessment of bone microarchitecture / Plenary speaker
International Symposium on Advances in Osteoporosis, Barcelona, Spain
2008 Fracture surrogates in osteoporosis / Plenary speaker
International Bone and Mineral Society Davos Workshops, Davos, Switzerland
2008 Bone strength assessment: from DXA to micro-imaging / Symposium Speaker at Symposium European Congress on Economic Aspects of Osteoporosis, Istanbul, Turkey (sponsored by Roche)
2008 Bone quality and bone strength / Plenary Speaker
Japanese Bone and Mineral Society Annual Meeting, Osaka, Japan
2008 Sex differences in bone structure and strength / Invited speaker
Osteomen: 4th International Conference on Osteoporosis in Men, San Margherita Ligure, Italy
2008 Non-invasive assessment of bone architecture and fracture risk / Meet-the-Professor session
International Osteoporosis Foundation World Congress on Osteoporosis, Bangkok, Thailand
Note: Congress was cancelled due to political turmoil
2008 Biomechanics of age-related fractures / Invited speaker
International Osteoporosis Foundation World Congress on Osteoporosis, Bangkok, Thailand.
Note: Congress was cancelled due to political turmoil
2009 Bone Structure and Function / Faculty Lecturer
17th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France.
2009 Biomechanics of Age-Related Fractures / Faculty Lecturer
17th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France.
2009 New Imaging Techniques for Assessing Bone Strength / Faculty Lecturer
17th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France.
2009 Bone Microarchitecture and Fracture Risk / Invited Speaker
2nd Joint Meeting of the International Bone and Mineral Society and Australian and New Zealand Bone and Mineral Society, Sydney, Australia.
2009 Effects of Anti-Resorptives and Bone Forming Agents on Bone Strength / Symposium Speaker
Annual Meeting of European Calcified Tissue Society, Vienna, Austria. (sponsored by Eli Lilly)
2009 Non-Invasive Assessment of Bone Strength in Osteoporosis / Invited Speaker
6th International Congress on Glucocorticoid Induced Osteoporosis, Siena, Italy.
2010 Contribution of Cortical Bone to Whole Bone Strength / Plenary Speaker
World Congress on Osteoporosis, Florence, Rome
2010 Bone Structure and Function / Faculty Lecturer
18th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France.
2010 Biomechanics of Age-Related Fractures / Faculty Lecturer
18th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France.
2010 New Imaging Techniques for Assessing Bone Strength / Faculty Lecturer
18th Annual Osteoporosis Training Course, International Osteoporosis Foundation, Lyon, France.
Report of Scholarship
Research Investigations:
1. Snow-Harter C, Bouxsein M, Lewis B, Charette S, Weinstein P, Marcus R. Muscle strength as a predictor of bone mineral density in young women. J Bone Min Res 1990; 5: 589-595.
2. Snow-Harter C, Bouxsein ML, Lewis BT, Carter DR, Marcus R. Effects of resistance and endurance exercise on bone mineral status of young women: A randomized exercise intervention trial. J Bone Min Res 1992; 7: 761-769.
3. Carter DR, Bouxsein ML, Marcus R. New interpretations of projected bone densitometry data. J Bone Min Res 1992; 7: 137-145.
4. Bouxsein ML, Myburgh KH, van der Meulen MCH, Lindenberger E, Marcus R. Age-related differences in cross-sectional geometry of the forearm bones in healthy women. Calcif Tissue Int 1994; 54:113-118.
5. Bouxsein ML, Courtney AC, Hayes WC. Ultrasound and densitometry of the calcaneus correlate with the failure loads of cadaveric femurs. Calcif Tissue Int 1995; 56: 99-103.
6. Moro M, Hecker AT, Bouxsein ML, Myers ER. Failure load of thoracic vertebrae correlates with lumbar bone mineral density measure by DXA. Calcif Tissue Int 1995; 56: 206-209.
7. Bouxsein ML, Radloff SE. Quantitative ultrasound of the calcaneus reflects the mechanical properties of calcaneal trabecular bone. J Bone Min Res 1996; 12: 839-846.
8. Lee SC, Coan BS, Bouxsein ML. Longitudinal ultrasound velocity of the tibia predicts the material properties of tibial cortical bone. Bone 1996; 21: 119-125.
9. Greenspan SL, Bouxsein ML, Melton ME, Kolodny AH, Clair JH, DeLuca PT, Stek M, Faulkner KG, Orwoll ES. Precision and discriminatory ability of calcaneal bone assessment techniques. J Bone Min Res 1997; 12: 1303-1313.
10. Bouxsein ML, Michaeli DA, Plass DB, Schick DA, Melton ME. Precision and accuracy of computed digital absorptiometry (CDA) for assessment of bone density of the hand. Osteoporosis Int 1997; 7: 444-449.
11. Michaeli DA, Mirshahi A, Singer F, Rapa F, Plass D, Bouxsein M. A new x-ray based osteoporosis screening tool provides accurate and precise assessment of phalanx bone mineral content. J Clin Densitometry 1999; 2:23-30.
12. Oden ZM, Selvitelli DM, Bouxsein ML. Effect of local density changes on the failure load of the proximal femur. J Orthop Res 1999; 16:661-667.
13. Bouxsein ML, Coan BS, Lee SC. Prediction of femoral strength by bone mineral density and quantitative ultrasound measurements of the heel and tibia. Bone 1999; 25: 49-54.
14. Bouxsein ML, Parker RA, Greenspan SL. Forearm bone mineral density cannot be used to predict the response to alendronate therapy. Osteoporosis Int 2000; 10: 505-509.
15. Turner CHT, Hsieh Y-F, Müller R, Bouxsein ML, Baylink DJ, Rosen CJ, Grynpas MD, Donahue LR, Beamer WG. Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Min Res 2000; 15: 1126-1131.
16. Nicholson PHF, Strelitzki R, Cleveland RO, Bouxsein ML. Scattering of ultrasound in cancellous bone: fundamental concepts and predictions from a theoretical model. J Biomechanics 2000; 33 (4): 503-506.
17. McClean RR, Hannan MT, Epstein BE, Bouxsein ML, Cupples LA, Murabito J, Kiel DP. Elderly cohort study subjects unable to return for follow-up have lower bone mass than those who can return. Am J Epidemiology 2000; 151: 689-692.
18. Nicholson PHF, Bouxsein ML. Quantitative ultrasound does not reflect mechanically induced damage in cancellous bone. J Bone Min Res 2000; 15:2467-2472.
20. Turner CHT, Hsieh Y-F, Müller R, Bouxsein ML, Rosen CJ, McCrann ME, Donahue LR, Beamer WG. Variation in bone biomechanical properties, microstructure and density in BxH recombinant inbred mice. J Bone Min Res. 2001; 16: 206-213.
21. Bouxsein ML, Turek TJ, Blake CA, Stevens ML, Li XJ, Seeherman HJ, Wozney JM. Recombinant human bone morphogenetic protein-2 accelerates osteotomy healing in rabbit model. J Bone Jt Surgery 2001; 83-A: 1219-1230.
22. Luppen CA, Blake CA, Ammirati KM, Stevens ML, Li XJ, Seeherman HJ, Wozney JM, Bouxsein ML. rhBMP-2 enhances osteotomy healing in glucocorticoid treated rabbits. J Bone Min Res 2002; 17: 301-310.
23. Bouxsein ML, Rosen CJ, Ackert CA, Shultz KL, Donahue LR, Adamo M, Powell DR. Turner CH, Müller RA, Beamer WG. Testing the relationship of IGF-1 to bone mineral density, skeletal morphology and fragility in vivo: Generation of a new congenic mouse strain. J Bone Min Res 2002; 17: 570-579.
24. Bouxsein ML, Palermo L, Yeung C, Black DM. Digital x-ray radiogrammetry predicts hip, wrist and vertebral fracture risk in elderly women: A prospective analysis from the Study of Osteoporotic Fractures. Osteoporosis Int 2002; 13: 358-365.
25. Nicholson PHF, Bouxsein ML. Effect of temperature on ultrasonic properties of the calcaneus in situ. Osteoporosis Int 2002; 13 (11): 888-892.
26. Nicholson PHF and Bouxsein ML. Bone marrow influences quantitative ultrasound measurements in human cancellous bone. Ultrasound in Medicine and Biology 2002; 28: 369-75.
27. Li G, Bouxsein ML, Luppen C, Li XJ, Wood M, Seeherman HJ, Wozney JM, Simpson H. Bone consolidation in enhanced by rhBMP-2 in a rabbit model of distraction osteogenesis. J Orthop Res 2002; 20: 779-788.
28. Shultz K, Donahue LR, Bouxsein ML, Baylink D, Rosen CJ, Beamer WG. Genetic decomposition of quantitative trait loci for high and low volumetric bone mineral density using congenic strains of mice. J Bone Min Res 2003; 18 (2) 175-85.
29. Zhang M, Xuan S, Bouxsein ML, von Stechow D, Faugere MC, Malluche H, Zhao G, Rosen CJ, Efstratiadis A, Clemens TL. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF-1 signaling in bone matrix mineralization. J Biol Chem 2002; 277 (46): 44005-12.
30. Muller ME, Webber CE, Bouxsein ML. Predicting the failure load of the distal radius. Osteoporosis Int 2003; 14: 345-52.
31. Babij P, Zhao W, Small C, Reddy PS, Yaworsky PJ, Bouxsein M, Bodine PVN, Robinson JA, Moran RA, Kharode Y, Bex F. High bone mass in transgenic mice expressing a mutant human low-density lipoprotein receptor related protein 5 (LRP5). J Bone Min Res 2003; 18: 960-974.
32. Bonner FJ, Sinaki M, Grabois M, Shipp KM, Lane JM, Lindsay R, Gold DT, Cosman F, Bouxsein ML, Weinstein JN, Gallagher RM, Melton LJ, Salcido RS, Gordon SL. Health professional’s guide to rehabilitation of the patient with osteoporosis. Osteoporosis Int 2003; 14 (suppl 2): S1-S22.
33. Einhorn TA, Majeska RJ, Mohaideen A, Kagel EM, Bouxsein ML, Turek TJ, Wozney JM. A single percutaneous injection of recombinant human bone morphogenetic protein-2 accelerates fracture repair. J Bone Jt Surg 2003; 85-A: 1425-35.
34. Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ. The effects of PTH and alendronate alone or in combination in post-menopausal osteoporosis. N Engl J Med 2003; 349 (13): 1207-1215.
35. Turner CH, Sun Q, Schriefer J, Pitner N, Price R, Bouxsein ML, Rosen CJ, Donahue LR, Shultz KL, Beamer WG. Congenic mice reveal gender-specific genetic regulation of femoral structure and strength. Calcif Tissue Int 2003; 73 (3): 297-303.
36. Li RH, Bouxsein ML, Blake CA, D’August D, Li XJ, Wozney JM, Kim H, Seeherman, HJ. rhBMP-2 injected in a calcium phosphate paste (a-BSM) accelerates healing in the rabbit ulnar osteotomy model. J Orthop Res 2003; 21 (6): 997-1004.
37. Tingart MJ, Bouxsein ML, Zurakowski DE, Warner JJP, Apreleva M. Three-dimensional distribution of bone density in the proximal humerus. Calcif Tissue Int 2003; 73 (6): 531-6.
38. Yakar S, Setser J, Zhao H, Atannard B, Haluzik M, Glatt V, Bouxsein M, Kopchick J, LeRoith D. Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1 deficient mice. J Clin Invest 2004; 113: 96-105.
39. Kacena M, Shivdasani RA, Wilson K, Yougen X, Troiano N, Nazarian A, Gundberg C, Bouxsein ML, Lorenzo JA, Horowitz MC. Unsuspected megakaryocyte-osteoblast interaction revealed through increased bone formation in mice deficient in transcription factors GATA-1 and NF-E2. J Bone Min Res 2004; 19:652-660.
40. Bouxsein ML, Uchiyama T, Rosen CJ, Shultz KL, Donahue LR, Turner CH, Sen S, Churchill G, Müller RA, Beamer, WG. Mapping quantitative trait loci for vertebral trabecular bone volume fraction and microarchitecture in mice. J Bone Min Res 2004; 19: 587-599.
41. Johnston JD, Small CF, Bouxsein ML, Pichora DR. Mechanical properties of the scapholunate ligament correlate with bone mineral density measurements of the hand. J Orthop Res 2004; 22 (4): 867-871.
42. Bertone AL, Pittman DD, Bouxsein ML, Li J, Clancy B, Seeherman HJ. Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model. J Orthop Res 2004; 22: 1261-70.
43. Seeherman H, Bouxsein M, Kim H, Li R, Li XJ, Aiolova M, Wozney JM. Recombinant human bone morphogenetic protein-2 delivered in an injectable calcium phosphate paste accelerates osteotomy healing in a nonhuman primate model. J Bone Jt Surg 2004 ; 86-A: 1961-72.
44. Bouxsein ML, Kaufman J, Tosi L, Cummings S, Lane J, Johnell O. Recommendations for care of the osteoporotic fracture patient to reduce the risk of future fracture. J Am Acad Orthop Surg 2004; 12 (6): 385-95.
45. Holmen SL, Giambernardi TA, Zylstra CR, Buckner-Berghaus BD, Resau JH, Hess JF, Glatt V, Bouxsein ML, Ai M, Warman ML, Williams BO. Decreased bone density and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Min Res 2004; 19: 2033-40.
46. Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S. Population-based study of age and sex differences in bone volumetric density, size, geometry and structure at different skeletal sites. J Bone Min Res 2004; 19:1945-54.
47. Rosen CJ, Ackert-Bicknell CL, Adamo ML, Shultz KL, Rubin J, Donahue LR, Horton LG, Delahunty KM, Beamer WG, Sipos J, Clemmons D, Nelson T, Bouxsein ML, Horowitz M. Congenic mice with low serum IGF-1 have increased body fat, reduce bone mineral density, and an altered osteoblast differentiation program. Bone, 2004; 35 (5): 1046-58.
48. Rosen CJ, Ackert-Bicknell C, Beamer WG, Nelson T, Adamo M, Cohen P, Bouxsein ML, Horowitz MC. Allelic differences in quantitative trait locus affecting insulin-like growth factor-I impact skeletal acquisition and body composition. Pediatr Nephrol, 2005; 20:255-260.
49. Bouxsein ML, Pierroz D, Glatt V, Goddard DS, Cavat F, Rizzoli R, Ferrari SL. Beta-arrestin2 regulates the differential response of cortical and trabecular bone to intermittent PTH in female mice. J Bone Min Res, 2005; 20:635-43.
50. Ferrari SL, Pierroz DD, Glatt V, Goddard DS, Bianchi EN, Lin FT, Manen D, Bouxsein ML. Bone response to intermittent parathyroid hormone is altered in mice null for ß-arrestin2. Endocrinology 2005; 146:1854-1862.
51. Knopp E, Troiano N, Bouxsein M, Sun BH, Lostritto K, Gundberg C, Dziura J, Insogna K. The effect of aging on the skeletal response to intermittent treatment with parathyroid hormone. Endocrinology 2005; 146: 1983-1990.
52. Bouxsein ML, Myers KS, Shultz KL, Donahue LR, Rosen CJ, Beamer WJ. Ovariectomy-induced bone loss varies among inbred strains of mice. J Bone Min Res 2005; 20 (7): 1085-92.
53. Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC, Bouxsein ML, Deng L, Clemens TL, Williams BO. Essential role of beta-catenin in post-natal bone acquisition. J Biol Chem 2005; 280 (22): 21162-8.
54. Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrin & Metab 2005; 90 (12): 6508-15.
55. Feng Y, Hsu YH, Terwedow H, Chen C, Xu X, Niu T, Zang T, Wu D, Tang G, Li Z, Hong X, Wang B, Brain JD, Cummings SR, Rosen C, Bouxsein ML, Xu X. Familial aggregation of bone mineral density and bone mineral content in a Chinese population. Osteop Int 2005: 16 (12): 1917-23.
56. Seeherman H, Li R, Bouxsein M, Kim H, Li XJ, Smith-Adaline E, Aiolova M, Wozney JM. rhBMP-2/calcium phosphate matrix accelerates osteotomy-site healing in a non-human primate model at multiple treatment times and concentrations. J Bone Jt Surg (Am) 2006; 88: 144-160.
57. Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, Oberg A, Rouleau PA, McCollough CH, Khosla S, Bouxsein ML. Population based analysis of the relationship of whole bone strength indices and fall-related loads to age- and sex-specific patterns of hip and wrist fractures. J Bone Min Res 2006; 21:315-23.
58. Hsu YH, Venners SA, Terwedow HA, Feng Y, Niu T, Li Z, Laird N, Brain JD, Cummings SR, Bouxsein ML, Rosen CJ, Xu X. Relationship of body composition, fat mass and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women. Am J Clin Nutr 2006; 83: 146-54.
59. Betz OB, Betz VM, Nazarian A, Pilapil CG, Vrahas MS, Bouxsein ML, Gerstenfeld LC, Einhorn TA, Evans, CH. Direct percutaneous gene delivery to enhance healing of segmental bone defects. J Bone Joint Surg (Am) 2006; 88:355-65.
60. Garnero P, Borel O, Gineyts E, Duboeuf F, Solberg H, Bouxsein ML, Christiansen C, Delmas PD. Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone 2006; 38: 300-9.
61. Yakar S, Bouxsein ML, Canalis E, Sun H, Glatt V, Gundberg C, Cohen P, Hwang D, Boisclair Y, Leroith D, Rosen CJ. The ternary IGF complex influences postnatal bone acquisition and the skeletal response to intermittent parathyroid hormone. Journal of Endocrinol 2006; 189 (2): 289-99.
62. Pierroz DP, Bouxsein ML, Rizzoli R, Ferrari SL. Combined treatment with a beta-blocker and intermittent PTH improves bone mass and microarchitecture in ovariectomized mice. Bone 2006; 39 (2): 260-7.
63. Viguet-Carrin S, Roux JP, Arlot ME, Merabet Z, Leeming J, Byrjalsen I, Delmas PD, Bouxsein ML. Contribution of the advanced glycation endproduct pentosidine and maturation of the collagen to compressive biomechanical properties of human lumbar vertebrae. Bone 2006; 39 (5): 1073-9.
64. Bouxsein ML, Riggs BL, Melton LJ III, Muller JA, Atkinson EJ, Oberg A, Robb RA, Camp JJ, Rouleau PA, McCollough CH, Khosla S. Biomechanical assessment of the age- and sex-related differences vertebral fragility: A population-based study using QCT. J Bone Min Res 2006; 21 (9): 1475-82.
65. Zalloua PA, Hsu YH, Terwedo H, Zang T, Wu D, Tang G, Li Z, Hong X, Azar ST, Wang B, Bouxsein ML, Brain J, Cummings SR, Rosen CJ, Xu X. Impact of seafood and fruit consumption on bone mineral density. Maturitas 2007; 56 (1): 1-11.
66. Hsu YH, Xu X, Terwedow HA, Niu T, Hung X, Wu D, Wang L, Brain JD, Bouxsein ML, Cummings SR, Rosen CJ. A large-scale genome-wide linkage analysis for loci linked to bone mineral density at different skeletal sites in extreme selected sibships. J Bone Min Res 2007; 22 (2): 184-194.
67. Notini A, McManus JF, Moore A, Bouxsein M, Jimenez M, Chiu WM, Glatt V, Kream BE, Handelsman DJ, Morris H, Zajac JD, Davey RA. Osteoblast deletion of exon 3 of the androgen receptor gene results in trabecular bone loss in adult male mice. J Bone Min Res 2007; 22 (3): 347-56.
68. Liu X, Bruxvoort KJ, Zylstra CR, Liu J, Cichowski R, Faugere M-C, Bouxsein ML, Wan C, Williams BO, Clemens TL. Lifelong accumulation of bone in mice lacking Pten in osteoblasts. Proc Natl Acad Sci 2007; 104 (7): 2259-64.
69. Yang D, Singh R, Divieti P, Guo J, Bouxsein ML, Bringhurst FR. Contributions of parathyroid hormone (PTH)/PTH-related peptide receptor signaling pathways to the anabolic effect of PTH on bone. Bone 2007; 40 (6): 1453-61.
70. Bouxsein ML, Szulc P, Munoz F, Thrall E, Sornay-Rendu E, Delmas PD. Contribution of trochanteric soft tissues to fall force estimates, the factor of risk, and prediction of hip fracture. J Bone Min Res 2007: 22(6): 25-31.
71. Wang Y, Wan C, Liu X, Cao X, Bouxsein ML, Faugere M-C, Guldberg RE, Gerstenfeld LC, Haase VH, Johnson RS, Schipani E, Clemens TL (2007) The hypoxia-inducible factor pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 2007; 117(6):1616-26.
72. Betz OB, Betz VM, Nazarian A, Egermann M, Gerstenfeld LC, Einhorn TA, Verhas MS, Bouxsein ML, Evans CH. Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects. Gene Ther 2007; 14 (13): 1039-44.
73. Glatt V, Canalis E, Stadmeyer L, Bouxsein ML. Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Min Res 2007; 22 (8): 1197-1207.
74. Tsiridis E, Morgan EF, Bancroft JM, Song M, Kain M, Gerstenfeld L, Einhorn TA, Bouxsein ML, Tornetta P. Effects of OP-1 and PTH in a new experimental model for the study of metaphyseal bone healing. J Orthop Res 2007; 25 (9): 1193-1203.
75. Melton LJ, Riggs BL, van Lenthe GH, Achenbach SJ, Muller R, Bouxsein ML, Amin S, Atkinson EJ, Khosla S. Contribution of in vivo structural measurements and load/strength ratios to the determination of forearm fracture risk in postmenopausal women. J Bone Min Res 2007; 22(9): 1442-8.
76. Kostenuik P, Ferrari S, Pierroz D, Bouxsein M, Morony S, Warmington KS, Adamu S, Geng Z, Grisanti M, Shalhoub V, Martin S, Biddlecome G, Shimamoto G, Boone T, Shen V.Lacey D. Infrequent delivery of a long-acting PTH-Fc fusion protein has potent anabolic effects on cortical and cancellous bone. J Bone Min Res 2007; 22 (10): 1534-47.
77. Melton LJ, Riggs BL, Keaveny TM, Achenbach SJ, Hoffman PF, Camp JJ, Rouleau PA, Bouxsein ML, Amin S, Atkinson EJ, Robb RA, Khosla S. Structural determinants of vertebral fracture risk. J Bone Min Res 2007, 22 (12): 1885-92.
78. Betz VM, Betz OB, Glatt V, Gerstenfeld LC, Einhorn TA, Bouxsein ML, Vrahas MS, Evans CH. Healing of segmental bone defects by direct percutaneous gene delivery: Effect of vector dose. Hum Gene Ther 2007; 18 (10): 907-15.
79. Betz OB, Betz VM, Nazarian A, Egermann M, Gerstenfeld LC, Einhorn TA, Vrahas MS, Bouxsein ML, Evans CH. Delayed administration of adenoviral BMP-2 improves the formation of bone in osseous defects. Gene Ther 2007; 14 (13): 1039-44.
80. Boutroy S, van Rietbergen B, Sornay-Rendu E, Munoz F, Bouxsein ML, Delmas PD. Finite element analysis based on in vivo HR-pQCT images of the distal radius is associated with wrist fracture in postmenopausal women. J Bone Min Res 2008; 23 (3): 392-99.
81. Mukherjee S, Raje N, Schoonmaker JA, Liu JC, Hideshima T, Wein MN, Jones DC, Vallet S, Bouxsein ML, Pozzi S, Chhetri S, Seo YD, Aronson JP, Patel C, Fulciniti M, Purton LE, Glimcher LH, Lian JB, Stein G, Anderson KC, Scadden DT. Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Inv 2008; 118 (2): 491-504.
82. McManus JF, Davey RA, Maclean HE, Doust EA, Chia WS, Sims NA, Bouxsein ML, Glatt V, Zajac JD, Danks JA. Intermittent Fugu parthyroid hormone 1 (1-34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats. Bone 2008; 42 (6): 1164-74.
83. Black DM, Bouxsein ML, Palermo L, McGowan JA, Newitt DC, Rosen E, Majumdar S, Rosen CJ. Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling. J Clin Endocrinol Metab 2008; 93 (6): 2166-72.
84. DeMambro VE, Clemmons Dr, Horton LG, Bouxsein ML, Wood TL, Beamer WG, Canalis E, Rosen CJ. Gender-specific changes in bone turnover and skeletal architecture in ifgbp-2 null mice. Endocrinology 2008; 149(5): 2051-61.
85. Rosental TD, Makhni EC, Day CS, Bouxsein ML. Improving evaluation and treatment for osteoporosis following distal radial fractures. A prospective randomized intervention. J Bone Joint Surg Am 2008; 90 (5): 953-61.
86. Pearsall RA, Canalis E, Corwall-Brady M, Underwood KW, Haigis B, Ucran J, Kumar R, Pobre E, Brinberg A, Werner ED, Glatt V, Stadmeyer L, Smith D, Seehra J, Bouxsein ML. A soluble activin type IIA receptor induces bone formation and improves skeletal integrity. Proc Natl Acad Sci USA 2008; 105 (19): 7082-7.
87. Shimada M, Greer PA, McMahon AP, Bouxsein ML, Schipani E. In vivo targeted deletion of calpain small subunit, Capn4, in cells of the osteoblast lineage impairs cell proliferation, differentiation, and bone formation. 2008; J Biol Chem 2008; 283 (30): 21002-10.
88. Davey RA, Turner AG, McManus JF, Chiu WSM, Tjahyono F, Moore AJ, Atkins GJ, Anderson PH, Ma C, Glatt V, MacLean HE, Vincent C, Bouxsein M, Morris HA, Findlay DM, Zajac JD. Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice. J Bone Min Res 2008; 23 (8); 1182-93.
89. Bouxsein ML and Delmas PD. Considerations for development of surrogate endpoints for anti-fracture efficacy of new treatments in osteoporosis: a perspective. J Bone Min Res 2008; 23 (8): 1155-67.
90. Wright LE, Christian PJ, Rivera Z, Van Alstine WG, Funk JL, Bouxsein ML, Hoyer PB. Comparison of skeletal effects of ovariectomy versus chemically-induced ovarian failure in mice. J Bone Min Res 2008; 23 (8):1296-1303.
91. Black DM, Bouxsein ML, Marshall LM, Cummings SR, Lang TF, Cauley JA, Ensrud KE, Nielson CM, Orwoll ES. Proximal femoral structure and the prediction of hip fracture in men: a large prospective study using quantitative computed tomography. J Bone Min Res; 2008; 23 (8): 1326-33.
92. O’Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR, Robling A, Bouxsein M, Schipani E, Turner CH, Jilka RL, Weinstein RS, Manolagas SC, Bellido T. Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS One 2008 Aug 13; 3 (8) e2942.
93. Keaveny TM and Bouxsein ML. Theoretical implications of the biomechanical fracture threshold. J Bone Min Res 2008; 23(10):1541-7.
94. Ackert-Bicknell CL, Demissie S, de Evsikova CM, Hsu YH, Demambro VE, Karasik D, Cupples LA, Ordovas JM, Tucker KL, Cho K, Canalis E, Paigen B, Churchill GA, Forejt J, Beamer WG, Ferrari S, Bouxsein ML, Kiel DP, Rosen CJ. A PPARG by dietary fat interaction influences bone mass in mice and humans. J Bone Min Res 2008; 23(9):1398-408.
95. Arlot M, Burt-Pichat B, Roux J, Vashisht D, Bouxsein M, Delmas PD. Microarchitecture influences microdamage accumulation in human vertebral trabecular bone. J Bone Min Res 2008; 23(10):1613-8.
96. Berman SD, Calo E, Landman AS, Danielian PS, Miller ES, West JC, Fonhoue BD, Caron A, Bronson R, Bouxsein ML, Mukherjee S, Lees JA. Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11851-6.
97. Brouwers JEM, Ruchelsman R, van Rietbergen B, Bouxsein ML. Influence of early and late zoledronic acid administration on vertebral structure and strength in ovariectomized rats. Calcified Tissue Int 2008; Sep;83(3):186-91.
98. Melton LJ 3rd, Riggs BL, Leibson CL, Achenbach SJ, Camp JJ, Bouxsein ML, Atkinson EJ, Robb RA, Khosla S. A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab 2008; 93(12): 4804-9
99. Okazaki M, Ferrandon S, Vilardaga JP, Bouxsein ML, Potts JT Jr, Gardella TJ. Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation. Proc Natl Acad Sci U S A. 2008; 105(43):16525-30.
100. Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Fukuda T, Mishina Y, Peterson RT, Block KD. BMP Type I receptor inhibition prevents ectopic ossification in a mouse model of fibrodysplasia ossificans progressiva. Nature Med 2008; Dec14(12):1363-9.
101. Bouxsein ML, Devlin MD, Glatt V, Dhillon H, Pierroz DP, Ferrari SL. Mice lacking ß-adrenergic receptors have increased bone mass, but are not protected from deleterious skeletal effects of ovariectomy. Endocrinology 2009. 150(1): 144-52.
102. Fajardo RJ, Cory E, Patel ND, Nazarian A, Laib A, Manoharan RK, Schmitz JE, Desilva JM, Maclatchy LM, Snyder BD, Bouxsein ML. Specimen size and porosity can introduce error into µCT-based tissue mineral density measurements. Bone 2009; 44(1):176-84
103. Yakar S, Rosen CJ, Bouxsein ML, Sun H, Mejia W, Kawashima Y, Wu Y, Emerton K, Williams V, Jepsen K, Schaffler MB, Majeska RJ, Gavrilova O, Gutierrez M, Hwang D, Pennisi P, Frystyk J, Boisclair Y, Pintar J, Jasper H, Domene H, Cohen P, Clemmons D, Leroith D. Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism. FASEB J 2009; 23(3):709-19.
104. Nielson CM, Bouxsein ML, Freitas SS, Ensrud KE, Orwoll ES; for the Osteoporotic Fractures in Men (MrOS) Research Group. Trochanteric soft tissue thickness and hip fracture in older men. J Clin Endocrinol Metab 2009; 94(2): 491-6.
105. Pierroz DD, Rufo A, Bianchi EN, Glatt V, Capulli M, Rucci N, Cavat F, Rizzoli R, Teti A, Bouxsein ML, Ferrari SL. Beta-arrestin2 regulates RANKL and Ephrins gene expression in response to bone remodeling in mice. J Bone Min Res 2009; 24(5); 775-84.
106. Rozental T, Vazquez M, Chacko A, Bouxsein ML. A comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. J Hand Surgery [Am] 2009; 34(4):595-602.
107. Brouwers JEM, Ruchelsman M, van Rietbergen B, Bouxsein ML. Determination of rat vertebral bone compressive fatigue properties in untreated intact rats and zoledronic acid treated, ovariectomized rats. Osteop Int 2009; 20(8):1377-84.
108. Kirmani S, Christen D, van Lenthe GH, Fischer PR, Bouxsein ML, McCready LK, Melton LJ, Riggs BL, Amin S, Muller R, Khosla S. Bone structure at the distal radius during adolescent growth. J Bone Min Res 2009; 24(6):1033-42.
109. Yakar S, Canalis E, Sun H, Mejia W, Kawashima Y, Nasser P, Courtland HW, Williams V, Bouxsein M, Rosen C, Jepsen KJ. Serum IFG-1 determines skeletal strength by regulating sub-periosteal expansion and trait interactions. J Bone Min Res 2009; 24(8): 1481-92.
110. Rozental TD, Vazquez MA, Chacko AT, Ayogu N, Bouxsein ML. Comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. J Hand Surg Am 2009; 34(4): 595-602.
111. Bouxsein M, Chen P, Glass E, Kallmes D, Delmas P, Mitlak B. Teriparatide and raloxifene reduce the risk of new adjacent vertebral fractures in postmenopausal women with osteoporosis: Results from two randomized, controlled trials. J Bone Jt Surg (Am) 2009; 91(6): 1321-28.
112. Sornay-Rendu E, Boutroy S, Munoz F, Bouxsein ML. Cortical and trabecular architecture are altered in postmenopausal women with fractures. Osteop Int 2009; 20(8): 1291-97.
113. Pozzi S, Vallet S, Mukherjee S, Cirstea D, Vaghela N, Santo L, Rosen E, Ikeda H, Okawa Y, Kiziltepe T, Schoonmaker J, Xie W, Hideshima T, Weller E, Bouxsein ML, Munshi NC, Anderson KC, Raje N. Clin Cancer Res; 15(18): 5829-39.
114. Borah B, Dufresne T, Nurre J, Phipps R, Chmielewski P, Wagner L, Lundy M, Bouxsein M, Zabeze R, Seeman E. Risedronate reduces intracortical porosity in women with osteoporosis. J Bone Min Res. 2010; 25(1):41-7.
115. Fritton JC, Emerton KB, Sun H, Kawashima Y, Mejia W, Wu Y, Rosen CJ, Panus D, Bouxsein ML, Majeska RJ, Schaffler MB, Yakar S. Growth hormone protects against ovariectomy-induced bone loss in states of low circulating IGF-1. J Bone Min Res. 2010; 25(2):235-46.
116. Roux J, Wegrzyn J, Arlot M, Guyen O, Delmas P, Chapurlat R, Bouxsein M. Contribution of trabecular and cortical components to biomechanical behavior of human vertebrae: an ex-vivo study. J Bone Miner Res. 2010; 25(2): 356-61.
117. Fajardo RJ, Manoharan RK, Pearsall RS, Davies MV, Marvell T, Monnell TE, Ucran JA, Pearsall AE, Khanzode D, Kumar R, Underwood KW, Roberts B, Seehra J, Bouxsein ML. Treatment with a soluble receptor for activin improves bone mass and structure in the axial and appendicular skeleton of female cynomolgus macaques (Macaca fascicularis). Bone. 2010; 46(1): 64-71.
118. Guo J, Liu M, Yang D, Bouxsein ML, Thomas CC, Schipani E, Bringhurst FR, Kronenberg HM. Phospholipase C signaling via the parathyroid hormone (PTH)/PTH-related peptide receptor is essential for normal bone responses to PTH. Endocrinology 2010; 151(8):3502-13.
119. Shomento SH, Wan C, Cao X, Faugere MC, Bouxsein ML, Clemens TL, Riddle RC 2010 Hypoxia-inducible factors 1alpha and 2alpha exert both distinct and overlapping functions in long bone development. J Cell Biochem 109(1):196-204.
120. Seeherman HJ, Li XJ, Bouxsein ML, Wozney JM. rhBMP-2 induces transient bone resorption followed by bone formation in a nonhuman primate core-defect model. J Bone Joint Surg (Am). 2010; 92(2):411-26.
121. Viguet-Carrin S, Follet H, Gineyts E, Roux JP, Munoz F, Chapurlat R, Delmas PD, Bouxsein ML. Association between collagen cross-links and trabecular microarchitecture properties of human vertebral bone. Bone 2010; 46(2):342-7.
122. Lotinun S, Pearsall RS, Davies MV, Marvell TH, Monnell TE, Ucran J, Fajardo RJ, Kumar R, Underwood KW, Seehra J, Bouxsein ML, Baron R 2010 A soluble activin receptor Type IIA fusion protein (ACE-011) increases bone mass via a dual anabolic-antiresorptive effect in Cynomolgus monkeys. Bone 46(4):1082-8.
123. Guo J, Liu M, Yang D, Bouxsein ML, Saito H, Galvin RJ, Kuhstoss SA, Thomas CC, Schipani E, Baron R, Bringhurst FR, Kronenberg HM. Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation. Cell Metab 2010; 11(2):161-71.
124. Roberts BJ, Thrall E, Muller J, Bouxsein ML. Comparison of hip fracture risk by femoral aBMD to Comparison of hip fracture risk prediction by femoral BMD and by the factor-of-risk for hip fracture derived from direct measurements of femoral strength. Bone. 2010; 46(3):742-6.
125. Devlin MJ, Cloutier AM, Thomas NA, Panus DA, Lotinun S, Pinz I, Baron R, Rosen CJ, Bouxsein ML. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. J Bone Miner Res 2010; 25(9):2078-88.
126. Wagner EB, Granzella NP, Saito H, Newman DJ, Young LR, Bouxsein ML. Partial weight suspension: a novel murine model for investigating adaptation to reduced musculoskeletal loading. J Appl Physiol 2010; 109(2):350-7.
127. Kiel DP, Hannan MT, Barton BA, Bouxsein ML, Lang TF, Brown KM, Shane E, Magaziner J, Zimmerman S, Rubin CT. Insights from the conduct of a device trial in older persons: low magnitude mechanical stimulation for musculoskeletal health. Clin Trials. 2010; 7(4):354-67.
128. Samelson EJ, Christiansen BA, Demissie S, Broe KE, Zhou Y, Meng CA, Yu W, Cheng X, O'Donnell CJ, Hoffmann U, Genant HK, Kiel DP, Bouxsein ML. Reliability of vertebral fracture assessment using multidetector CT lateral scout views: the Framingham Osteoporosis Study. Osteoporos Int 2010 (in press).
129. Chantry AD, Heath D, Mulivor AW, Pearsall S, Baud'huin M, Coulton L, Evans H, Abdul N, Werner ED, Bouxsein ML, Key ML, Seehra J, Arnett TR, Vanderkerken K, Croucher P. Inhibiting activin-A signaling stimulates bone formation and prevents cancer induced bone destruction in vivo. J Bone Miner Res. 2010 (in press)
130. Wegrzyn J, Roux JP, Arlot ME, Boutroy S, Vilayphiou N, Guyen O, Delmas PD, Chapurlat R, Bouxsein ML. Role of trabecular microarchitecture and its heterogeneity parameters in the mechanical behavior of ex-vivo human L3 vertebrae. J Bone Miner Res. 2010 (in press)
131. Iyer S, Christiansen BA, Roberts BJ, Valentine MJ, Manoharan RK, Bouxsein ML. A biomechanical model for estimating loads on thoracic and lumbar vertebrae. Clin Biomech (Bristol, Avon). 2010 (in press)
132. Jones M, Liu JC, Barthel TK, Hussain S, Lovria E, Cheng D, Schoonmaker JA, Mulay S, Ayers DC, Bouxsein ML, Stein GS, Mukherjee S, Lian JB. A Proteasome Inhibitor, Bortezomib, Inhibits Breast Cancer Growth and Reduces Osteolysis by Downregulating Metastatic Genes. Clin Cancer Res. 2010 (in press)
Other Peer-Reviewed Publications:
1. Bouxsein ML. Technology insight: non-invasive assessment of bone strength in osteoporosis. Nature Clinical Practice Rheumatology 2008, 4: 310-318.
2. Rosen CJ, Bouxsein ML. Is osteoporosis obesity of bone? Nature Clinical Practice Rheumatology; 2006: 2: 1-9.
3. Engelke K, Adams JE, Armbrecht G, Augat P, Bogado CE, Bouxsein ML, Felsenberg D, Ito M, Prevrhal S, Hans DB, Lewiecki EM. Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions. J Clin Densitom. 2008 Jan-Mar;11(1):123-62.
4. Bouxsein ML and Seeman E. Quantifying the material and structural determinants of bone strength. In Best Practice and Research Clinical Rheumatology. Best Pract Res Clin Rheumatology. 2009; 23 (6): 741-53.
5. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010; 25(7):1468-86.
Reviews, Chapters, Monographs, and Editorials:
1. Bouxsein ML, Marcus R. Overview of Exercise and Bone Mass. In Rheumatic Disease Clinics of North America. ed: N Lane, WB Saunders, Inc., Philadelphia; 1994. vol 20 (3), p 787-802.
2. Bouxsein ML, Myers ER, Hayes WC. Biomechanics of Age-Related Fractures. In Osteoporosis. ed: R Marcus, J Kelsey, and D Feldman, Academic Press, Inc., San Diego; 1995. p 373-393.
3. Hayes WC, Bouxsein ML. Biomechanics of Cortical and Trabecular Bone: Implications for Assessment of Fracture Risk. In Basic Orthopedic Biomechanics. ed. VC Mow and WC Hayes, Raven Press, Ltd., New York; 1997. P 69-112.
4. Bouxsein ML, Augat P. Biomechanics of Bone. In The Assessment of Bone Status Using Quantitative Ultrasound. ed: CF Njeh, D Hans, T Fuerst, HK Genant, Martin Dunitz Publishers, London; 1999. p 21-46.
5. Nicholson PHF, Bouxsein ML. Ultrasound measurements in vitro: cortical bone. In The Assessment of Bone Status Using Quantitative Ultrasound. ed: CF Njeh, D Hans, T Fuerst, HK Genant, Martin Dunitz Publishers, London; 1999. p 177-194.
6. Bouxsein ML. Application of Biomechanics to the Aging Human Skeleton. In The Aging Skeleton. eds: C Rosen, J Glowacki, J Bilezikian, Academic Press, Inc, San Diego; 1999. p 315-331.
7. Bouxsein ML. Biomechanics of Age-Related Fractures. In The Atlas of Clinical Endocrinology. Ed: R Marcus, Current Medicine, Inc, Philadelphia, PA; 1999. p 139-145.
8. Bouxsein ML. Biomechanics of Age-Related Fractures. In Osteoporosis IIe. ed: R Marcus, J Kelsey, and D Feldman, Academic Press, Inc., San Diego; 2001, p 509-534.
9. Nelson D, Bouxsein ML. Exercise maintains bone mass, but do people maintain exercise? Invited editorial for the Journal of Bone and Mineral Res. 2001, 16:202-205.
10. Bouxsein ML. Technical Aspects of Skeletal Assessment Using Quantitative Ultrasound. In Osteoporosis: Pathophysiology and Clinical Management”, ed: E Orwoll and M Bliziotes, Humana Press, Totowa, NJ; 2002.
11. Bouxsein ML, Jepsen KJ. Biomechanics of Age-Related Fractures. In The Atlas of Clinical Endocrinology. Ed: E. Orwoll, Current Medicine, Inc, Philadelphia, PA; 2003.
12. Bouxsein ML. Bone Quality: where do we go from here? Osteop Int, 2003; 14 (suppl 5): 118-127.
13. Bouxsein ML. Mechanisms of Osteoporosis Therapy: A Bone Strength Perspective. In Clinical Cornerstone, Elsevier, Hillsborough NJ; 2003.
14. Bouxsein ML. Non-invasive measurements of bone strength: Promise and Peril. J Musculoskel Neuron Interact, 2004; 4(4): 404-5.
15. Bouxsein ML. Determinants of Skeletal Fragility. In Best Practice & Research, Clinical Rheumatology. Ed: D. Reid and P. Geusens, Rapid Medical Media, Eastbourne, East Sussex, UK; 2005, 19(6): 897-912.
16. Bouxsein ML and Karasik D. Bone geometry and skeletal fragility. Current Osteoporosis Reports; 2006: 4 (4): 49-56.
17. Bouxsein ML. Biomechanics of osteoporotic fractures. Clinical Reviews in Bone and Mineral Metabolism, 2006; 4 (3): 143-54.
18. Bouxsein ML. Biomechanics of Age-Related Fractures. In Osteoporosis IIIe. ed: R Marcus, J Kelsey, C Rosen and D Feldman, Academic Press, Inc., San Diego; 2007, p 601-616
19. Marcus R and Bouxsein ML. The Nature of Osteoporosis. In Osteoporosis IIIe. ed: R Marcus, J Kelsey, C Rosen and D Feldman, Academic Press, Inc., San Diego; 2007, p 27-33.
20. Morgan EF and Bouxsein ML. Biomechanics of Bone and Age-Related Fractures. In Principles of Bone Biology, ed: J Bilizikian, L Raisz, TJ Martin, Academic Press, Inc, San Diego; 2008 (in press)
21. Bouxsein ML and Delmas PD. Vertebral fracture status, assessed using standard densitometry equipment, predicts incident fractures in elderly women. Nat Clin Pract Endocrinol Metab. 2008 Dec;4(12):652-3.
22. Christiansen BA and Bouxsein ML. Assessment of bone mass and microarchitecture in rodents. In Primer on Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7th Edition. Ed: CJ Rosen, American Society for Bone and Mineral Research, Washington, DC; 2008, p 38-44.
23. Christiansen BA and Bouxsein ML Biomechanics of vertebral fractures and the vertebral fracture cascade. Curr Osteoporos Rep 2010; 8(4):198-204.
Letters to the Editor:
1. Bouxsein M, Fajardo RJ. Letter to the editor: Cortical stability and hip fracture risk. Lancet, 2005: 366: 1523-4.
Thesis:
Bouxsein ML. Physical Activity and Bone Density [PhD dissertation] Stanford University, 1992
Nonprint Materials:
“Take Action Now” — DVD Presentation on Osteoporosis for Primary Care Physician, sponsored by the Alliance for Better Bone Health, September 2004. Distributed to over 3000 primary care physicians across United States.
Other:
Watts N, Bouxsein ML and Raisz L. “Understanding the relationships among bone strength, fracture risk and the effects of antiresorptive therapy.” A CME white paper, jointly sponsored by the University of Cincinnati and IMED Communications. Released April 2006.
Bouxsein ML. “Bone quality and osteoporotic fracture”, in Osteoporosis: Clinical Updates, published by the National Osteoporosis Foundation, Spring 2007.
Abstracts:
Narrative Report
• The purpose of the narrative is to provide a concise description of your major contributions and achievements to those outside your immediate field. The narrative should be integrative, demonstrating the connections across the variety of activities in which you engage. It should be written in the first person. It should be limited to 500 words
• In general, we suggest the following structure for the narrative:
o An opening paragraph that provides an overall summary of your major activities and achievements. Include an estimate of the proportion of your effort dedicated to teaching, research, clinical service, administrative activities and other relevant professional roles
o Description of achievements in your Area of Excellence (Investigation, Teaching and Educational Leadership, or Clinical Expertise and Innovation); may include a description of work in progress such as pending grants or manuscripts in preparation
o Description of contributions to Teaching and Education (if not your area of excellence). This may include a description of mentorship activities not discussed elsewhere in the CV
o Description of contributions in Significant Supporting Activities, if any
o A final paragraph that integrates and summarizes the contributions described above
I received my PhD in Mechanical Engineering from Stanford University under the co-mentorship of a two professors, one in the engineering school and one in the medical school. My thesis research involved the study of how exercise affects the skeleton, from a mechanical and biological view, and ultimately led me to focus my research efforts in the biomechanics of osteoporosis and age-related fractures. My early exposure to clinical issues in osteoporosis have guided my research interests. In one of my first manuscripts, co-published with my two advisors in 1992, we described limitations of the gold-standard method for clinical assessments of bone density. The concepts presented in that article are still relevant today, as evidenced by the growing interest in “bone quality” and methods to assess it. During my post-doctoral fellowship I continued to study the biomechanics of age-related fractures, focusing on the utility of a new technique, quantitative ultrasound, as a tool for predicting fracture risk. I then chose to enhance my ability to understand biologic mechanisms underlying skeletal fragility and repair, and for 5 years worked part-time as a research scientist at Genetics Institute. In this position, I gained greater knowledge of animal models of disease, and published key papers on the ability of bone morphogenetic protein to enhance fracture healing. Overall, my research has focused on 1) clinical investigations of the pathophysiology of osteoporosis and the use of novel tools for prediction of fracture risk and monitoring treatment efficacy, 2) the use of mouse models to explore the genetic determinants of skeletal fragility, and 3) use of animal models to study fracture healing, the structural origins of skeletal fragility, and the efficacy of osteoporosis therapies.
My major contributions have been in translating engineering concepts of how and why age-related fractures occur, as well as how osteoporosis therapies reduce fracture risk, to a clinical audience. This contribution has taken the form of manuscripts, book chapters, and numerous invitations to lecture on this topic both in the US and internationally. I have been recognized as a leader in the field of biomechanics as it relates to the etiology and treatment of osteoporotic fractures, as evidenced by invitations to speak at the NIH and FDA Conference on Biomarkers and Surrogate Endpoints, the NIH-sponsored Consensus Conference on Osteoporosis, and the NIH-sponsored conference on Skeletal Genetics. Recently, I have had the opportunity to lead several efforts in furthering knowledge of osteoporotic fractures by serving on the steering committee which organized a congress on “Bone Quality” sponsored jointly by the NIH and the ASBMR. As a follow-up to that meeting, I also served on the steering committee which organized a 2-day meeting between academic investigators, FDA, NIH and industry representatives to identify research needs and possible collaborative efforts in the area of bone strength assessment. Furthermore, I have served on several committees charged with raising the awareness of orthopedic surgeons about osteoporosis and thereby improving the care of fragility fracture patients. To this end, Dr. Tosi and I drafted the position statement that was approved in June 2003 by the Board of Directors of the American Academy of Orthopaedic Surgeons titled “Recommendations for Improving Care of the Fragility Fracture Patient”. I was also the lead author on a set of recommendations for improving the care of the fragility fracture patient that was published in the Journal of the American Academy of Orthopedic Surgeons.
C. Report of Current Research Activities
Biomechanics of Osteoporotic Fractures
Our long-term objectives are to understand the etiology of osteoporotic fractures and mechanisms of osteoporosis therapies, and to develop and evaluate technologies that may be used for widespread diagnosis of osteoporosis and assessment of fracture risk. Thus, in addition to studying factors that influence bone strength, I have evaluated and continue to evaluation non-invasive assessments of skeletal strength, including image analysis of forearm and hand radiographs, quantitative ultrasound, and 3D QCT — with respect to their abilities to predict the mechanical properties of bone and, ultimately, fracture risk. Moreover, I have focused on understanding the contribution of skeletal loading to fracture risk. I believe that understanding both the skeletal loads as well as bone strength are critical for optimal fracture risk assessment and prevention. My work in this area have included both laboratory studies using human cadaveric specimens, as well as clinical investigations within epidemiologic cohorts and randomized clinical trials.
For example, vertebral fractures are the most common osteoporotic fracture, occurring in 1/3 of women and 1/6 of men over age 50. They cause significant morbidity and increased mortality, and are among the strongest risk factors for future fractures. Despite the high and growing occurrence, personal and societal costs, the biomechanical mechanisms that underlie vertebral fractures remain obscure, in particular why they occur preferentially at the mid-thoracic and thoraco-lumbar regions of the spine. We showed that the ratio of skeletal loading to bone strength explains much of the age- and sex-specific patterns of fractures. Thus, we propose that a better understanding of the mechanisms underlying vertebral fracture can be gained by a biomechanical approach that relates the loads applied to the spine to vertebral strength at specific regions along the spine. Our overall hypothesis is that the age-, sex- and location-specific patterns of vertebral fracture can be explained by assessing the ratio between vertebral strength and spinal loading. To address this, we are using an age- and sex-stratified sample of 3D quantitative computed tomography (QCT) scans of the thoracic and lumbar spine from 3529 men and women (aged 31 – 83), enrolled in the “Framingham Heart Study Offspring and Third Generation Multidetector CT Study” to compare the ratio of spine load to vertebral strength (ie, the factor-of-risk), in men and women, across the lifespan, and along the spine. In addition, will use the cohort to conduct a case-control study comparing the factor-of-risk in persons over age 50 with and without prevalent vertebral fractures. This study will provide novel information about vertebral fractures, because despite the high occurrence of fractures in the thoracic spine, no population-based studies have assessed age- and sex-related variation in vertebral strength and/or spine loading in the thoracic region. This population-based study will provide new insights into the pathophysiology of vertebral fractures by employing a biomechanical approach to fracture risk assessment, and by studying, for the first time, bone density and geometry and trunk muscle morphology in both the thoracic and lumbar spine in men and women over a wide age range. The findings will have important public health implications, as a better understanding of the interaction between bone density, geometry and spinal loading may lead to improved diagnosis of individuals at risk for fracture and to targeted therapeutic interventions for prevention and treatment of vertebral fractures.
Genetic Analysis of Bone Microarchitecture and Strength
While many environmental factors (i.e., diet and exercise) affect bone accumulation during growth, studies in twins indicate that about 60-70% of the variability in bone mineral density is genetically determined. Moreover, it ha been suggested that the variable rate of bone loss among women after the menopause is due to genetic factors. One useful strategy for uncovering the complex gene interactions contributing to bone fragility employs inbred strains differing in bone mineral density and bone strength. Individuals within an inbred strain are “identical twins” and their environments can be closely controlled. Planned matings between strains allow segregation of alleles important for bone strength and/or bone mineral density. Knowledge of strong synteny between the mouse and human genomes affords opportunities to use these mouse models to expand our knowledge of human disease. Thus, in this project, which represents a collaboration between the Jackson Laboratory and our laboratory at BIDMC, we trying to identify the genetic factors regulating bone microarchitecture and strength, as well as the skeletal response to estrogen deficiency and aging using inbred mice.
Role of ß-Arrestin2 in Mediating the Skeletal Response to PTH
Osteoporosis is a common condition that presently affects more than 30 million elderly persons in the US alone. Several osteoporosis therapies that inhibit bone loss have been shown to increase bone mineral density and reduce fracture risk. However, the ultimate benefits of these anti-resorptive drugs may be limited. Therefore alternative therapies that induce new bone formation, such as parathyroid hormone (PTH), need to be developed. In humans, PTH is the major regulator of calcium and phosphate homeostasis, and plays a central role in bone metabolism. Although PTH therapy appears promising as an anabolic treatment for osteoporosis, much of cell and molecular physiology underlying the biologic effects of PTH is unknown, including the molecular basis for the observation that continuous high-dose administration of PTH causes predominantly osteoclastic resorption, whereas lower intermittent doses elicit anabolic effects.
The biological actions of PTH are mediated by the human PTH/PTH-related protein (PTHrP) receptor (PTH1Rc), which is a G protein-coupled receptor (GPCR). Activation of this receptor by PTH in vitro leads to a rapid interaction of the receptor with an intracellular adaptor molecule, ß-arrestin2. This interaction is crucial in the regulation of intracellular signaling and cellular endocytosis of the PTH1Rc—ligand complex. Therefore, to better understand the in vivo regulation of the anabolic effects of PTH in bone, we are conducting a series of experiments using mice with a deletion of the ß-arrestin2 gene (ßarr-2 KO) and transgenic mice with targeted overexpression of ß-arrestin2 in bone cells, including characterization of skeletal structure and mineral metabolism during normal growth, as well as the skeletal and mineral metabolic response to exogenous PTH. The results of these in vivo experiments will provide direct evidence for the physiologic role of ß-arrestin 2 in regulating the biologic activity of PTH in bone. Hence, insights gained from these studies will likely provide potential new avenues for the rational development of therapies for metabolic bone diseases such as osteoporosis and hyperparathyroidism.
Effects of treatments and/or genetic manipulation on bone microarchitecture and strength
We were among the first groups to establish the use of high-resolution microcomputed tomography for assessment of bone microarchitecture in rodent models. As such, we have performed and continue to conduct studies examining the skeletal effects of therapeutic interventions and/or genetic manipulation. These studies are performed in collaboration with investigators throughout the world, who gain from my knowledge in skeletal phenotyping, as well as study design and interpretation. We have established an array of outcome assessments for these types of analyses, including: high resolution microcomputed tomography, in vivo and ex vivo dual-energy x-ray absorptiometry, and bone biomechanical testing.
Professional and Educational Leadership Role: National
2001-02 Member of Steering Committee to Develop Guidelines for Rehabilitation in Osteoporosis
The charge of this multi-disciplinary committee was to develop recommendations for rehabilitation in patients with osteoporosis. Recommendations were published in Osteoporosis International in 2003.
Bonner FJ, Sinaki M, Grabois M, Shipp KM, Lane JM, Lindsay R, Gold DT, Cosman F, Bouxsein ML, Weinstein JN, Gallagher RM, Melton LJ, Salcido RS, Gordon SL. Health professional’s guide to rehabilitation of the patient with osteoporosis. Osteoporosis Int 2003; 14 (suppl 2): S1-S22.
2003-04 Member of Steering Committee, World Osteoporosis Orthopedic Organization
The goal of this committee of was to develop guidelines to enhance care of fragility fracture patients. Recommendations were published in the Journal of the American Academy of Orthopedic Surgeons in 2004.
Bouxsein ML, Kaufman J, Tosi L, Cummings S, Lane J, Johnell O. Recommendations for care of the osteoporotic fracture patient to reduce the risk of future fracture. J Am Acad Orthop Surg 2004; 12 (6): 385-95.
2004-05 Member of Steering Committee: ASBMR and NIH Jointly Sponsored Meeting on Bone Quality
This 6-person committee was charged with developing the program for a meeting on Bone Quality that was jointly sponsored by the National Institutes of Health and the American Society for Bone and Mineral Research. The meeting was held in Bethesda in May 2005, and was attended by over 500 individuals.
2005 Member of Steering Committee: NIH Sponsored Meeting on Bone Quality and Industry Partnerships
This 7-person committee was charged with organizing a meeting between academic, FDA and industry representatives to explore possible collaborative efforts in the area of bone quality and development of surrogate markers for fracture risk. The meeting was held in December 2005 in Bethesda, and was attended by approximately 100 individuals.
2008- Member of Steering Committee: NIH Sponsored Task Force on Standardization of Bone Structure and Density Assessment
The goals of this 5-person committee are to 1) determination and prioritize needs with regard to standardization of terminology and nomenclature used to describe outcome variables for various imaging techniques; 2) develop approaches for standardization of image acquisition and analysis algorithms for key variables from each technique; and 3) present to the community at large any resulting proposals for discussion and feedback.
2008- Member of Steering Committee: National Osteoporosis Foundation’s International Symposium on Osteoporosis
The task of this committee is to develop the scientific program for the NOF’s 8th International Symposium on Osteoporosis.
Professional and Educational Leadership Role: International
2004- Faculty, International Osteoporosis Foundation Course on Osteoporosis
Dr. Bouxsein is a faculty member for the Osteoporosis Training Course, sponsored annually by the International Osteoporosis Foundation. This 3-day course enrolls ~ 200 students per year. Preparation time 20 hours, contact time 10 hours.
2004-06 Co-chair of the Orthopedic Surgeons Initiative, International Osteoporosis Foundation
The charge of this committee is to improve the care of fragility fracture patients by 1) educational initiatives targeted at orthopedic surgeons; 2) policy changes amongst medical providers and regulatory agencies; and 3) research projects to improve fracture outcomes among osteoporotic patients. An educational slide kit was developed in collaboration with the Bone and Joint Decade and the International Society for Fracture Repair, and 5000 copies distributed at orthopaedic meetings worldwide.
2007- Co-chair of the Bone Quality and Bone Imaging Working Group, International Osteoporosis Foundation
The goals of this group are to broaden the awareness of advanced imaging techniques by developing educational slide sets, to critically evaluate techniques that may serve as surrogates for fracture risk, and to identify research needs in this area.
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