Bone Cell Biology - Columbia University...Bone remodeling: relationship to the amount and structure...
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1 Bone Cell Biology David W. Dempster, PhD Professor of Clinical Pathology Columbia University Bone Remodeling Bone Remodeling “The skeleton, out of site and often out of mind, is a formidable mass of tissue occupying about 9% of the body by bulk and no less than 17% by weight. The stability and immutability of dry bones and their persistence for centuries and even millions of years after the soft tissues have turned to dust give us a false impression of bone during life. Its fixity after death is in sharp contrast to its ceaseless activity during life” A. Cooke, Lancet 1955 “The skeleton, out of site and often out of mind, is a formidable mass of tissue occupying about 9% of the body by bulk and no less than 17% by weight. The stability and immutability of dry bones and their persistence for centuries and even millions of years after the soft tissues have turned to dust give us a false impression of bone during life. Its fixity after death is in sharp contrast to its ceaseless activity during life” A. Cooke, Lancet 1955 Christian Cemetery, Nordby, Denmark, 1050- 1250 A.D. Poulsen et al, Bone 2001 Christian Cemetery, Nordby, Denmark, 1050- 1250 A.D. Poulsen et al, Bone 2001
Transcript of Bone Cell Biology - Columbia University...Bone remodeling: relationship to the amount and structure...
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Bone Cell BiologyDavid W. Dempster, PhD
Professor of Clinical PathologyColumbia University
Bone RemodelingBone Remodeling“The skeleton, out of site and often out of mind, is a formidable
mass of tissue occupying about 9% of the body by bulk and no less than 17% by weight. The stability and immutability of dry bones and their persistence for centuries and even millions of years after the soft tissues have turned to dust give us a falseimpression of bone during life. Its fixity after death is in sharp contrast to its ceaseless activity during life”A. Cooke, Lancet 1955
“The skeleton, out of site and often out of mind, is a formidablemass of tissue occupying about 9% of the body by bulk and no less than 17% by weight. The stability and immutability of dry bones and their persistence for centuries and even millions of years after the soft tissues have turned to dust give us a falseimpression of bone during life. Its fixity after death is in sharp contrast to its ceaseless activity during life”A. Cooke, Lancet 1955
Christian Cemetery, Nordby, Denmark, 1050-1250 A.D.
Poulsen et al, Bone 2001
Christian Cemetery, Nordby, Denmark, 1050-1250 A.D.
Poulsen et al, Bone 2001
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Cancellous and Cortical Bone
Remodeling Participates in Mineral Homeostasis
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Remodeling Maintains Mechanical Strength
The Remodeling Cycle
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Bone Remodeling
Osteoclast
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Osteoclast
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Human Osteoclast
The Remodeling Cycle
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Reversal
The Remodeling Cycle
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Formation
Osteoblast
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Osteoblasts
Osteoblasts and Osteoid Osteocyte
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Osteocyte – the Mechanosensor
Marotti G, 1996.
Formation Completed
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Resting
Cancellous Bone Packets
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Cortical Bone Remodeling Cycle
Haversian Systems
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Duration of Remodeling Cycle
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Remodeling Balance on Different Envelopes
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Changes in Bone With Age
Frost HM. Clin Orthop Relat Res. 1985;200:198-225.
8 year 20 year 60 year
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The Importance of Bone Geometry for Cortical Bone Strength
• In general, wide tubes are stronger than narrow tubes due to a greater cross-sectional moment of inertia (CSMI)
Bike frames are strong due to wide tubing
Periosteal expansion helps to maintain
bone strength as we age
Ferretti JL et al. Bone. 1996;18:97-102.
Central Axis
Periosteum
Endosteum
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MALE
FEMALE
AGINGBEFOREPUBERTY
DURING PUBERTY
NEUTRALLONG AXIS
PERIOSTEAL ENVELOPE
ENDOCORTICAL ENVELOPE
YOUNG
FEMALE MALE
NEUTRALLONG AXIS
ELDERLY
PERIOSTEAL DIAMETER
ENDOCORTICAL DIAMETER
FEMALE MALE
Courtesy of E. Seeman.
Effect of Aging on Cortical Bone
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R. McNeill Alexander, 2004
Origin of Bone Cells
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Dr. Dempster’s Osteoclasts
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Osteoporosis
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Progression of Osteoporosis – Three Generations
Photo credit: Geoff Higgs, MD, courtesy eMotion pictures –An Exhibition of Orthopedics in Art
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Mechanisms of Cancellous Bone Loss
Slow Loss
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20 30 40 50 60 70 80 90
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FemaleMale
Rapid Loss
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1. Meunier P et al. Clin Endocrinol Metab. 1973;2:239-256.2. Parfitt AM. Bone remodeling: relationship to the amount and structure of bone and the pathogenesis
and prevention. In: Riggs BL, Melton LV, eds. Osteoporosis: Etiology, Diagnosis, and Management. New York: Raven;1988:45-94
Old BoneNew Bone
Can
cello
us b
one
volu
me
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Age (years)
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Mechanisms of Cancellous Bone Loss
Slow Loss
1010
20 30 40 50 60 70 80 90
30
25
20
15
FemaleMale
Rapid Loss
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2
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1. Meunier P et al. Clin Endocrinol Metab. 1973;2:239-256.2. Parfitt AM. Bone remodeling: relationship to the amount and structure of bone and the pathogenesis
and prevention. In: Riggs BL, Melton LV, eds. Osteoporosis: Etiology, Diagnosis, and Management. New York: Raven;1988:45-94
Old BoneNew Bone
Can
cello
us b
one
volu
me
(%)
Age (years)
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Trabecular Plate Perforation
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Normal Cancellous Bone
Osteoporotic Cancellous Bone
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Bisected Trabecular Rod
Normal Osteoporosis
© 2000, David W. Dempster, PhD.
MICROARCHITECTURAL CHANGES IN OSTEOPOROSIS
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Architectural Changes in Osteoporosis
Normal Remodeling Cycle
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Trabecular Plate Perforation
Disconnection of A Trabecular Rod
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IL-6 Stimulates Osteoclastogenesis
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Osteoclast Formation, Activation and Survival Inhibited
Activated Osteoclast
CFU-M
Pre-Fusion Osteoclast
MultinucleatedOsteoclast
Bone
Osteoblast
Growth Factors HormonesCytokines
RANK
RANKL
OPG
Osteoclast Activated
Osteoclast Regulation by RANK Ligand and Osteoclast Regulation by RANK Ligand and Osteoprotegerin (OPG) Osteoprotegerin (OPG)
CFU-M
CFU-M = colony forming unit macrophage
Effects of RANKL on Trabecular Bone in theProximal Tibia
YY Yuan. ASBMR Meeting. Abstract #SA357
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RANKL
PTHEstrogen
Estrogen
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Normal Bone Biopsy Compared to Male Osteoporosis
Normal biopsy compared to Primary Hyperparathyroidism
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Osteomalacia
Tetracycline Labeling – Abnormal Mineralization
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Paget’s Disease
Paget’s Disease – Tetracycline Labels
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