Bone Cell Biology. David W. Dempster, PhD. Professor of Clinical Pathology Columbia University. Bone Remodeling

Transcription

1 Bone Cell Biology David W. Dempster, PhD Professor of Clinical Pathology Columbia University 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 Christian Cemetery, Nordby, Denmark, A.D. Poulsen et al, Bone

2 Cancellous and Cortical Bone Remodeling Participates in Mineral Homeostasis 2

3 Remodeling Maintains Mechanical Strength The Remodeling Cycle 3

4 Osteoclast 4

5 Osteoclast Human Osteoclast 5

6 The Remodeling Cycle Reversal 6

7 The Remodeling Cycle Formation 7

8 Osteoblast Osteoblasts 8

9 Osteoblasts and Osteoid Osteocyte Osteocyte the Mechanosensor Marotti G,

10 Formation Completed Resting 10

11 Cancellous Bone Packets Cortical Bone Remodeling Cycle 11

12 Haversian Systems 12

13 Duration of Remodeling Cycle Remodeling Balance on Different Envelopes 13

14 Changes in Bone With Age 8 year 20 year 60 year Frost HM. Clin Orthop Relat Res. 1985;200: 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 Periosteum Central Axis Endosteum Periosteal expansion helps to maintain bone strength as we age Ferretti JL et al. Bone. 1996;18:

15 R. McNeill Alexander, 2004 Effect of Aging on Cortical Bone BEFORE PUBERTY DURING PUBERTY AGING PERIOSTEAL ENVELOPE ENDOCORTICAL ENVELOPE PERIOSTEAL DIAMETER MALE NEUTRAL LONG AXIS ENDOCORTICAL DIAMETER FEMALE YOUNG NEUTRAL LONG AXIS FEMALE MALE ELDERLY FEMALE MALE Courtesy of E. Seeman

16 Origin of Bone Cells 16

17 Dr. Dempster s Osteoclasts 17

18 Osteoporosis Progression of Osteoporosis Three Generations Photo credit: Geoff Higgs, MD, courtesy emotion pictures An Exhibition of Orthopedics in Art 18

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20 Mechanisms of Cancellous Bone Loss 1 2 Cancellous bone volume (%) Female Male Age (years) Slow Loss 3 Rapid Loss Old Bone New Bone 1. Meunier P et al. Clin Endocrinol Metab. 1973;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:

21 Mechanisms of Cancellous Bone Loss 1 2 Cancellous bone volume (%) Female Male Age (years) Slow Loss 3 Rapid Loss Old Bone New Bone 1. Meunier P et al. Clin Endocrinol Metab. 1973;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: Trabecular Plate Perforation 21

22 Normal Cancellous Bone 22

23 Osteoporotic Cancellous Bone Bisected Trabecular Rod 23

24 MICROARCHITECTURAL CHANGES IN OSTEOPOROSIS Normal Osteoporosis 2000, David W. Dempster, PhD. Architectural Changes in Osteoporosis 24

25 Normal Remodeling Cycle Trabecular Plate Perforation 25

26 Disconnection of A Trabecular Rod 26

27 IL-6 Stimulates Osteoclastogenesis 27

28 Osteoclast Regulation by RANK Ligand and Osteoprotegerin (OPG) CFU-M OPG RANKL RANK Growth Factors Hormones Cytokines Osteoblast Pre-Fusion Osteoclast Multinucleated Osteoclast Activated Osteoclast Bone CFU-M = colony forming unit macrophage Osteoclast Activated Osteoclast Formation, Activation and Survival Inhibited 28

29 Effects of RANKL on Trabecular Bone in the Proximal Tibia YY Yuan. ASBMR Meeting. Abstract #SA357 Estrogen Glucocorticoids PTH RANKL Glucocorticoids PTH Estrogen 29

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35 Normal Bone Biopsy Compared to Male Osteoporosis Normal biopsy compared to Primary Hyperparathyroidism 35

36 Osteomalacia Tetracycline Labeling Abnormal Mineralization 36

37 Paget s Disease Paget s Disease Tetracycline Labels 37

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