Principles of Bone Biology

1898 Pages·2019·95.317 MB·English

by  John Bilezikian (editor), T. John Martin (editor), Thomas L. Clemens (editor), Clifford J. Rosen (editor)

Principles of Bone Biology
Fourth Edition
Volume 1
Edited by
John P. Bilezikian
Division of Endocrinology, Department of Medicine
College of Physicians and Surgeons
Columbia University, New York, NY, United States
T. John Martin
St. Vincent’s Institute of Medical Research;
Department of Medicine at St. Vincent’s Hospital
The University of Melbourne
Melbourne, Australia
Thomas L. Clemens
Department of Orthopaedic Surgery
Johns Hopkins University School of Medicine;
Baltimore Veterans Administration Medical Center
Baltimore, MD, United States
Clifford J. Rosen
Maine Medical Center Research Institute
Scarborugh, ME, United States
Principles of Bone Biology
Fourth Edition
Volume 2
Edited by
John P. Bilezikian
Division of Endocrinology, Department of Medicine
College of Physicians and Surgeons
Columbia University, New York, NY, United States
T. John Martin
St. Vincent’s Institute of Medical Research;
Department of Medicine at St. Vincent’s Hospital
The University of Melbourne
Melbourne, Australia
Thomas L. Clemens
Department of Orthopaedic Surgery
Johns Hopkins University School of Medicine;
Baltimore Veterans Administration Medical Center
Baltimore, MD, United States
Clifford J. Rosen
Maine Medical Center Research Institute
Scarborugh, ME, United States
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Dedication of Fourth Edition
to Lawrence G. Raisz
Bytheendofthe1970s,whentheboneresearchcommunityfeltthatitwasreadyforitsownscientificsociety,LarryRaisz
was one of the leaders of the group that founded the American Society for Bone and Mineral Research (ASBMR). The
ASBMR had its first annual conference in 1979, with Larry serving as its second president. As the first editor of the
Journal of Bone and Mineral Research, for a decade, Larry set the highest scientific standards for quality and integrity.
That standard remains untarnished today.
Larry’s knowledge of the facts in our field was prodigious. His expertise and experience in basic elements of bone
biology were exceptional. He had great understanding and wisdom in interpretation of the clinical implications of basic
bonebiology.Buthealwayswantedtoknowmore.AtASBMRandotherannualmeetings,itwasalwaysLarrywhorose
to the microphone after a presentation to ask, not only the first question, but typically the best one! Remarkably, Larry
could translatebasic bonebiologytotheclinical arena. Few inourfieldthen ornow could so smoothlyintegrate clinical
aspectsofmetabolicbonediseaseswiththeburgeoningknowledgeofunderlyingpathophysiologicalmechanisms.Adding
to these talents was a collegiality and an exuberant enthusiasm that pervaded all venues of Larry Raisz’s world. As
osteoporosis became more widely recognized to be a medical scourge, then and now, Larry quickly grasped the need to
speak about the burden of the disease and contributed to the international dialogue, raising awareness among us all. This
awareness was a major factor in the recognition among countries that we are dealing with a disease that needs greater
understanding at all levels. And, indeed, at all levels, Larry contributed so much.
These qualities made Larry Raisz a wonderfully effective coeditor of the first three editions of Principles of Bone
Biology.Muchmorethanthat,though,hewasapleasuretoworkwithasacolleagueandfriend,exceptionallyefficientand
withunfailinghumorandoptimismwhenfacedwithanyadversity.Larrywouldsharethehighsandlowswithyou,butthe
lows were rare and short lived.
WerememberhimconstantlyanddedicatetoLawrenceG.Raisz,MD,thisfourtheditionofwhathecalled“BigGray.”
John P. Bilezikian
T. John Martin
Thomas L. Clemens
Clifford J. Rosen
List of Contributors
DavidAbrahamCentreforRheumatologyandConnective George Bou-Gharios Institute of Ageing and Chronic
Tissue Diseases, University College London, London, Disease, University of Liverpool, Liverpool, United
United Kingdom Kingdom
Maria Almeida Division of Endocrinology and Metabo- Roger Bouillon Laboratory of Clinical and Experimental
lism, Center for Osteoporosis and Metabolic Bone Endocrinology, Department of Chronic Diseases,
Diseases, University ofArkansas forMedicalSciences, Metabolism and Aging, KU Leuven, Belgium
Little Rock, AR, United States; The Central Arkansas Mary L. Bouxsein Center for Advanced Orthopaedic
Veterans Healthcare System, Little Rock, AR, United
Studies, Beth Israel Deaconess Medical Center, Bos-
States
ton, MA, United States; Department of Orthopaedic
Elena Ambrogini Center for Osteoporosis and Metabolic Surgery, Harvard Medical School, Boston, MA, Uni-
Bone Diseases, University of Arkansas for Medical ted States; Endocrine Unit, Department of Medicine,
Sciences Division of Endocrinology and Metabolism, Massachusetts General Hospital, Boston, MA, United
Little Rock, AR, United States; Central Arkansas Vet- States
erans Healthcare System, Little Rock, AR, United Brendan F. Boyce Department of Pathology and Labo-
States
ratory Medicine, University of Rochester School of
Andrew Arnold Center for Molecular Oncology and Medicine and Dentistry, Rochester, NY, United States
Division of Endocrinology and Metabolism, University Steven Boyd McCaig Institute for Bone and Joint Health,
of Connecticut School of Medicine, Farmington, CT,
The University of Calgary, Calgary, AB, Canada
United States
Maria Luisa Brandi Department of Experimental and
Bence Bakos 1st Department of Medicine, Semmelweis
Clinical Biomedical Sciences, University of Florence,
University Medical School, Budapest, Hungary
Florence, Italy
Clemens Bergwitz Departments of Pediatrics and Internal DavidB. Burr DepartmentofAnatomyandCell Biology,
Medicine, Yale University School of Medicine, New
Indiana Center for Musculoskeletal Health, Indiana
Haven, CT, United States
University School of Medicine, Indianapolis, IN, Uni-
Daniel D. Bikle VA Medical Center and University of ted States
California San Francisco, San Francisco, California, Laura M. Calvi Department of Medicine and Wilmot
United States
CancerCenter,UniversityofRochesterMedicalCenter,
JohnP.BilezikianDivisionofEndocrinology,Department Rochester, NY, United States
of Medicine, College of Physicians and Surgeons, Ernesto Canalis Departments of Orthopaedic Surgery and
Columbia University, New York, NY, United States
Medicine, and the UConn Musculoskeletal Institute,
Neil Binkley University of Wisconsin School of Medicine UConn Health, Farmington, CT, United States
and Public Health, Madison, Wisconsin, United States XuCaoDepartmentofOrthopedicSurgery,JohnsHopkins
Alessandro Bisello Department of Pharmacology and UniversitySchoolofMedicine,Baltimore,MD,United
Chemical Biology, Laboratory for GPCR Biology, States
University of Pittsburgh School of Medicine, Pitts- Geert Carmeliet Laboratory of Clinical and Experimental
burgh, PA, United States
Endocrinology, Department of Chronic Diseases,
L.F.BonewaldIndianaCenterforMusculoskeletalHealth, Metabolism and Ageing, KU Leuven, Leuven, Bel-
Departments of Anatomy and Cell Biology and Ortho- gium; Prometheus, Division of Skeletal Tissue Engi-
paedic Surgery, Indiana University, Indianapolis, IN, neering, KU Leuven, Leuven, Belgium
USA
xiii
xiv List of Contributors
Thomas O. Carpenter Departments of Pediatrics and Benoit de Crombrugghe The University of Texas M.D.
InternalMedicine,YaleUniversitySchoolofMedicine, Anderson Cancer Center, Houston, TX, United States
New Haven, CT, United States Hector F. DeLuca Department of Biochemistry, Uni-
Wenhan Chang Endocrine Research Unit, Department of versity of WisconsineMadison, Madison, Wisconsin,
Veterans Affairs Medical Center, Department of Med- United States
icine, University of California, San Francisco, CA, David W. Dempster Regional Bone Center, Helen Hayes
United States
Hospital, West Haverstraw, NY, United States;
Shek Man Chim Regeneron Pharmaceuticals, Inc. Tarry- Department of Pathology and Cell Biology, College of
town, NY, United States Physicians and Surgeons, Columbia University, New
Shilpa Choudhary Department of Medicine and Muscu- York, NY, United States
loskeletal Institute, UConn Health, Farmington, CT, Matthew T. Drake Department of Endocrinology and
United States Kogod Center of Aging, Mayo Clinic College of
Sylvia Christakos Department of Microbiology, Bio- Medicine, Rochester, MN, United States
chemistryandMolecularGenetics,Rutgers,NewJersey Patricia Ducy Department of Pathology & Cell Biology,
Medical School, Newark, NJ, United States Columbia University, College of Physicians & Sur-
Yong-Hee Patricia Chun Department of Periodontics, geons, New York, NY, United States
University of Texas Health Science Center at San FrankH.EbetinoDepartmentofChemistry,Universityof
Antonio, San Antonio, TX, United States Rochester, Rochester, NY, United States; Mellanby
Cristiana Cipriani Department of Internal Medicine and Centre for Bone Research, Medical School, University
of Sheffield, United Kingdom
Medical Disciplines, Sapienza University of Rome,
Italy Klaus Engelke Department of Medicine, FAU University
Roberto Civitelli Washington University in St. Louis, Erlangen-Nürnberg and Universitätsklinikum Erlangen,
Erlangen, Germany; Bioclinica, Hamburg, Germany
DepartmentofMedicine,DivisionofBoneandMineral
Diseases, St. Louis, MO, United States Reinhold G. Erben Department of Biomedical Research,
Thomas L. Clemens Department of Orthopaedic Surgery, University of Veterinary Medicine Vienna, Vienna,
Austria
Johns Hopkins University School of Medicine, Balti-
more, MD, United States; Baltimore Veterans Admin- David R. Eyre Department of Orthopaedics and Sports
istration Medical Center, Baltimore, MD,UnitedStates Medicine, University of Washington, Seattle, WA,
Michael T. Collins Skeletal Disorders and Mineral United States
Homeostasis Section, National Institute of Dental and Charles R. Farber Center for Public Health Genomics,
Craniofacial Research, National Institutes of Health, Departments of Public Health Sciences and Bio-
Bethesda, MD, United States chemistry and Molecular Genetics, University of
Caterina Conte Vita-Salute San Raffaele University, Virginia School of Medicine, Charlottesville, VA,
United States
Milan, Italy; Division of Immunology, Transplantation
andInfectiousDiseases,IRCCSSanRaffaeleScientific MarinaFeigensonDepartmentofDevelopmentalBiology,
Institute, Milan, Italy Harvard School of Dental Medicine, Boston, MA,
Mark S. Cooper The University of Sydney, ANZAC United States
Research Institute and Department of Endocrinology & Mathieu Ferron Institut de Recherches Cliniques de
Metabolism,ConcordHospital,Sydney,NSW,Australia Montréal, Montréal, QC, Canada
Jillian Cornish Department of Medicine, University of Pablo Florenzano Endocrine Department, School of
Auckland, Auckland, New Zealand Medicine, Pontificia Universidad Católica de Chile,
Serge Cremers Department of Pathology & Cell Biology Santiago, Chile
and Department of Medicine, Vagelos College of Francesca Fontana Washington University in St. Louis,
Physicians and Surgeons, Columbia University Irving DepartmentofMedicine,DivisionofBoneandMineral
Medical Center, United States Diseases, St. Louis, MO, United States
Bess Dawson-Hughes Jean Mayer USDA Human Nutri- Brian L. Foster Biosciences Division at College of Den-
tion Research Center on Aging at Tufts University, tistry at Ohio State University, Columbus, OH, United
Boston, Massachusetts, United States States
List of Contributors xv
Peter A. Friedman Department of Pharmacology and FadilM.HannanDepartmentofMusculoskeletalBiology,
Chemical Biology, Laboratory for GPCR Biology, Institute of Ageing and Chronic Disease, Faculty of
University of Pittsburgh School of Medicine, Pitts- Health & Life Sciences, University of Liverpool, Liv-
burgh, PA, United States erpool, United Kingdom; Academic Endocrine Unit,
Seiji Fukumoto Fujii Memorial Institute of Medical Sci- Radcliffe Department of Medicine, University of
Oxford,OxfordCentreforDiabetes,Endocrinologyand
ences, Institute of Advanced Medical Sciences,
Metabolism (OCDEM), Churchill Hospital, Oxford,
Tokushima University, Tokushima, Japan
United Kingdom
LauraW. Gamer DepartmentofDevelopmentalBiology,
StephenE.HarrisDepartmentofPeriodontics,University
Harvard School of Dental Medicine, Boston, MA,
of Texas Health Science Center at San Antonio, San
United States
Antonio, TX, United States
Thomas J. Gardella Endocrine Unit, Department of
Iris R.HartleyInterinstitute Endocrine TrainingProgram,
Medicine and Pediatric Nephrology, MassGeneral
Eunice Kennedy Shriver National Institute of Child
Hospital for Children, Massachusetts General Hospital
Health and Human Development, National Institutes of
and Harvard Medical School, Boston, MA, United
Health, Bethesda, MD, United States
States
Patrick Garnero INSERM Research Unit 1033-Lyos, Christine Hartmann Institute of Musculoskeletal Medi-
cine, Department of Bone and Skeletal Research,
Lyon, France
MedicalFacultyoftheUniversityofMünster,Münster,
Harry K. Genant Departments of Radiology and Medi-
Germany
cine, University of California, San Francisco, CA,
Robert P. Heaney Creighton University, Omaha, NE,
United States
United States
FrancescaGiustiDepartmentofExperimentalandClinical
Geoffrey N. Hendy Metabolic Disorders and Complica-
Biomedical Sciences, University of Florence, Florence,
tions, McGill University Health Center Research Insti-
Italy
tute, and Departments of Medicine, Physiology and
Andy Göbel Department of Medicine III, Technische Uni-
Human Genetics, McGill University, Montreal, QC,
versität Dresden, Dresden, Germany; German Cancer
Canada
Consortium (DKTK), Partner site Dresden and German
Matthew J. Hilton Department of Orthopaedic Surgery,
Cancer Research Center (DKFZ), Heidelberg, Germany
DepartmentofCellBiology,DukeUniversitySchoolof
David Goltzman Calcium Research Laboratories and
Medicine, Durham, NC, United States
DepartmentofMedicine,McGillUniversityandMcGill
Lorenz C. Hofbauer Center for Regenerative Therapies
University Health Centre, Montreal, QC, Canada
Dresden, Center for Healthy Aging and Division of
Jeffrey P. Gorski Department of Oral and Craniofacial
Endocrinology, Diabetes, and Bone Diseases, Depart-
Sciences, School of Dentistry, and Center for Excel-
ment of Medicine III, Technische Universität Dresden,
lence in Mineralized and Dental Tissues, University of
Dresden, Germany
MissourieKansasCity,KansasCity,MO,UnitedStates
Gill Holdsworth Bone Therapeutic Area, UCB Pharma,
James Griffith Department of Imaging and Interventional
Slough, United Kingdom
Radiology, The Chinese University of Hong Kong,
Yi-Hsiang Hsu Department of Medicine, Beth Israel
Hong Kong, China
Deaconess Medical Center and Harvard Medical
R. Graham G Russell Mellanby Centre for Bone
School, Harvard School of Public Health, Hinda and
Research, Medical School, University of Sheffield,
Arthur Marcus Institute for Aging Research, Hebrew
UnitedKingdom;NuffieldDepartmentofOrthopaedics,
SeniorLife, Boston, MA, United States
Rheumatology and Musculoskeletal Sciences, The
DavidM.HudsonDepartmentofOrthopaedicsandSports
Oxford University Institute of Musculoskeletal Scien-
ces,The BotnarResearch Centre, NuffieldOrthopaedic Medicine, University of Washington, Seattle, WA,
United States
Centre, Oxford, United Kingdom
Kurt D. Hankenson Department of Orthopaedic Surgery, Marja Hurley Department of Medicine, University of
Connecticut School of Medicine, UConn Health,
University of Michigan Medical School, Ann Arbor,
Farmington, CT, United States
MI, United States
xvi List of Contributors
Karl L. Insogna Departments of Pediatrics and Internal Yasuhiro Kobayashi Institute for Oral Science, Matsu-
Medicine, Yale University School of Medicine, New moto Dental University, Nagano, Japan
Haven, CT, United States Martin Konrad Department of General Pediatrics, Uni-
Robert L. Jilka Center for Osteoporosis and Metabolic versityChildren’sHospitalMünster,Münster,Germany
Bone Diseases, University of Arkansas for Medical Paul J. Kostenuik Phylon Pharma Services, Newbury
Sciences Division of Endocrinology and Metabolism,
Park, CA, United States; School of Dentistry, Uni-
Little Rock, AR, United States; Central Arkansas Vet-
versity of Michigan, Ann Arbor, MI, United States
eransHealthcareSystem,LittleRock,AR,UnitedStates
Christopher S. Kovacs Faculty of Medicine, Memorial
Mark L. Johnson Department of Oral and Craniofacial University of Newfoundland, St. John’s, NL, Canada
Sciences, UMKC School of Dentistry, Kansas City,
Richard Kremer Calcium Research Laboratories and
MO, United States
DepartmentofMedicine,McGillUniversityandMcGill
RachelleW.JohnsonVanderbiltCenterforBoneBiology,
University Health Centre, Montreal, QC, Canada
Department of Medicine, Division of Clinical Pharma-
Venkatesh Krishnan Lilly Research Laboratories, Eli
cology, Nashville, TN, United States
Lilly&Company,LillyCorporateCenter,Indianapolis,
Glenville Jones Department of Biomedical and Molecular
United States
Science, Queen’s University, Kingston, ON, Canada
Henry M. Kronenberg Endocrine Unit, Massachusetts
Stefan Judex Department of Biomedical Engineering,
General Hospital, Harvard Medical School, Boston,
BioengineeringBuilding,StateUniversityofNewYork
MA, United States
at Stony Brook, Stony Brook, NY, United States
Peter A. Lakatos 1st Department of Medicine, Semmel-
HaraldJüppnerEndocrineUnit,DepartmentofMedicine
weis University Medical School, Budapest, Hungary
and Pediatric Nephrology, MassGeneral Hospital for
Uri A. Liberman Department of Physiology and Phar-
Children, Massachusetts General Hospital and Harvard
macology, Sackler Faculty of Medicine, Tel Aviv
Medical School, Boston, MA, United States
University, Tel-Aviv, Israel
Ivo Kalajzic Department of Reconstructive Sciences,
Joseph A. Lorenzo The Departments of Medicine and
UConn Health, Farmington, CT, United States
Orthopaedics, UConn Health, Farmington, CT, United
Gérard Karsenty Department of Genetics and Develop-
States
ment,ColumbiaUniversityMedicalCenter,NewYork,
Conor C. Lynch Department of Tumor Biology, Moffitt
NY, United States
Cancer Center, Tampa, FL, United States
Hua Zhu Ke Angitia Biopharmaceuticals Limited,
Karen M. Lyons Department of Orthopaedic Surgery/
Guangzhou, China
Orthopaedic Hospital, University of California, Los
Sundeep Khosla Department of Medicine, Division of
Angeles, CA, United States; Department of Molecular,
Endocrinology, Mayo Clinic College of Medicine, Cell, & Developmental Biology, University of Cal-
Rochester, MN, United States; The Robert and Arlene
ifornia, Los Angeles, CA, United States
KogodCenteronAging,Rochester,MN,UnitedStates
Y.LindaMaBiotechnologyandAutoimmunityResearch,
Douglas P. Kiel Department of Medicine, Beth Israel
Eli Lilly and Company, Indianapolis, IN, United States
Deaconess Medical Center and Harvard Medical
Christa Maes Laboratory of Skeletal Cell Biology and
School, Harvard School of Public Health, Hinda and
Physiology(SCEBP),SkeletalBiologyandEngineering
Arthur Marcus Institute for Aging Research, Hebrew
Research Center (SBE), KU Leuven, Leuven, Belgium
SeniorLife, Boston, MA, United States
J. Klein-Nulend Department of Oral Cell Biology, Michael Mannstadt Endocrine Unit, Massachusetts Gen-
eral Hospital, Harvard Medical School, Boston, MA,
Academic Centre for Dentistry Amsterdam (ACTA),
United States
University of Amsterdam and Vrije Universiteit
Amsterdam, Amsterdam Movement Sciences, Amster- Stavros Manolagas Division of Endocrinology and
dam, The Netherlands Metabolism, Center for Osteoporosis and Metabolic
Frank C. Ko Center for Advanced Orthopaedic Studies, Bone Diseases, University of Arkansas for Medical
Sciences, Little Rock, AR, United States; The Central
Beth Israel Deaconess Medical Center, Boston, MA,
ArkansasVeteransHealthcareSystem,LittleRock,AR,
United States
United States
List of Contributors xvii
RobertMarcusStanfordUniversity,Stanford,CA,United Nicola Napoli Unit of Endocrinology and Diabetes, Uni-
States versity Campus Bio-Medico, Rome, Italy; Division of
DavidE.MaridasDepartmentofDevelopmentalBiology, Bone and Mineral Diseases, Washington University in
St Louis, St Louis, MO, United States
Harvard School of Dental Medicine, Boston, MA,
United States TallyNaveh-ManyMinervaCenterforCalciumandBone
Pierre J. Marie UMR-1132 Inserm (Institut nationalde la Metabolism,NephrologyServices,HadassahUniversity
Hospital, Hebrew University School of Medicine, Jer-
SantéetdelaRechercheMédicale)andUniversityParis
usalem, Israel
Diderot, Sorbonne Paris Cité, Paris, France
Francesca Marini Department of Experimental and Clin- Edward F. Nemeth MetisMedica, Toronto, ON, Canada
ical Biomedical Sciences, University of Florence, ThomasL.Nickolas DivisionofNephrology,Department
Florence, Italy of Medicine, Columbia University Medical Center,
Jasna Markovac California Institute of Technology, New York, NY, United States
Pasadena, CA, United States Michael S. Ominsky Radius Health Inc., Waltham, MA,
T. John Martin St. Vincent’s Institute of Medical United States
Research, Melbourne, Australia; Department of Noriaki Ono Department of Orthodontics and Pediatric
Medicine at St. Vincent’s Hospital, The University of Dentistry, University of Michigan School of Dentistry,
Melbourne, Melbourne, Australia Ann Arbor, MI, United States
BryaG.MatthewsDepartmentofMolecularMedicineand David M. Ornitz Department of Developmental Biology,
Pathology, University of Auckland, Auckland, New Washington University School of Medicine, St. Louis,
Zealand MO, United States
Antonio Maurizi Department of Biotechnological and Nicola C. Partridge Department of Basic Science and
Applied Clinical Sciences, University of L’Aquila, Craniofacial Biology, New York University College of
L’Aquila, Italy Dentistry, New York, NY, United States
SasanMirfakhraeeTheUniversityofTexasSouthwestern VihitabenS.PatelDepartmentofBiomedicalEngineering,
Medical Center, Department of Internal Medicine, BioengineeringBuilding,StateUniversityofNewYork
Endocrine Division, Dallas, TX, United Sates at Stony Brook, Stony Brook, NY, United States
SharonM.MoeDivisionofNephrology,IndianaUniversity J.WesleyPikeDepartmentofBiochemistry,Universityof
School of Medicine, Rodebush Veterans Administration WisconsineMadison, Madison, WI, United States
Medical Center, Indianapolis, IN, United States Carol Pilbeam Department of Medicine and Muscu-
David G. Monroe Department of Medicine, Division of loskeletal Institute, UConn Health, Farmington, CT,
Endocrinology, Mayo Clinic College of Medicine, United States
Rochester, MN, United States; The Robert and Arlene Lori Plum Department of Biochemistry, University of
KogodCenteronAging,Rochester,MN,UnitedStates WisconsineMadison,Madison,Wisconsin,UnitedStates
Carolina A. Moreira Bone Unitof Endocrine Division of John T. Potts, Jr. Endocrine Unit, Department of
Federal University of Parana, Laboratory PRO, Section
Medicine and Pediatric Nephrology, MassGeneral
of Bone Histomorphometry, Pro Renal Foundation,
Hospital for Children, Massachusetts General Hospital
Curitiba, Parana, Brazil
and Harvard Medical School, Boston, MA, United
Ralph Müller Institute for Biomechanics, ETH Zurich, States
Zurich, Switzerland J. Edward Puzas Department of Orthopaedics and Reha-
David S. Musson Department of Medicine, University of bilitation, University of Rochester School of Medicine
Auckland, Auckland, New Zealand and Dentistry, Rochester, NY, United States
Teruyo Nakatani Department of Basic Science and Cra- Tilman D. Rachner Department of Medicine III, Techni-
niofacial Biology, New York University College of sche Universität Dresden, Dresden, Germany; German
Dentistry, New York, NY, United States Cancer Consortium (DKTK), Partner site Dresden and
Dorit Naot Department of Medicine, University of Auck- German Cancer Research Center (DKFZ), Heidelberg,
Germany; Center for Healthy Aging and Division of
land, Auckland, New Zealand