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

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volu

me

(%)

Age (years)

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Mechanisms of Cancellous Bone Loss

Slow Loss

1010

20 30 40 50 60 70 80 90

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25

20

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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

(%)

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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