Bone Remodeling Bone Cell Biology David W. Dempster, PhD Professor of Clinical Pathology Columbia University 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 Cancellous and Cortical Bone Remodeling Participates in Mineral Homeostasis Remodeling Maintains Mechanical Strength The Remodeling Cycle 1
Osteoclast Osteoclast Human Osteoclast The Remodeling Cycle Reversal 2
The Remodeling Cycle Formation Osteoblast Osteoblasts Osteoblasts and Osteoid Osteocyte Osteocyte the Mechanosensor Marotti G, 1996. 3
Formation Completed Resting Cancellous Bone Packets Cortical Bone Remodeling Cycle Haversian Systems 4
Duration of Remodeling Cycle Remodeling Balance on Different Envelopes Changes in Bone With Age 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) 8 year 20 year 60 year Bike frames are strong due to wide tubing Periosteum Periosteal expansion helps to maintain bone strength as we age Central Axis Endosteum Frost HM. Clin Orthop Relat Res. 1985;200:198-225. 27 Ferretti JL et al. Bone. 1996;18:97-102. 28 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 R. McNeill Alexander, 2004 NEUTRAL LONG AXIS FEMALE MALE ELDERLY FEMALE MALE Courtesy of E. Seeman. 30 5
Origin of Bone Cells Dr. Dempster s Osteoclasts Osteoporosis Progression of Osteoporosis Three Generations Photo credit: Geoff Higgs, MD, courtesy emotion pictures An Exhibition of Orthopedics in Art 6
Mechanisms of Cancellous Bone Loss 1 2 Cancellous bone volume (%) 30 25 20 15 10 10 Female Male 20 30 40 50 60 70 80 90 Age (years) Slow Loss 3 Rapid Loss Old Bone New Bone 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 39 Mechanisms of Cancellous Bone Loss 1 2 Cancellous bone volume (%) 30 25 20 15 10 10 Female Male 20 30 40 50 60 70 80 90 Age (years) Trabecular Plate Perforation Slow Loss 3 Rapid Loss Old Bone New Bone 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 41 7
Normal Cancellous Bone Osteoporotic Cancellous Bone Bisected Trabecular Rod MICROARCHITECTURAL CHANGES IN OSTEOPOROSIS Architectural Changes in Osteoporosis Normal Osteoporosis 2000, David W. Dempster, PhD. 8
Normal Remodeling Cycle Trabecular Plate Perforation Disconnection of A Trabecular Rod IL-6 Stimulates Osteoclastogenesis 9
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 Effects of RANKL on Trabecular Bone in the Proximal Tibia Estrogen Glucocorticoids PTH RANKL Glucocorticoids PTH Estrogen YY Yuan. ASBMR Meeting. Abstract #SA357 10
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Normal biopsy compared to Primary Hyperparathyroidism Normal Bone Biopsy Compared to Male Osteoporosis Osteomalacia Tetracycline Labeling Abnormal Mineralization 12
Paget s Disease Tetracycline Labels Paget s Disease 13