Scientific Article   |    
Mechanisms Responsible for Longitudinal Growth of the Cortex: Coalescence of Trabecular Bone into Cortical Bone
Edwin R. Cadet, MD; Rachel I. Gafni, MD; Edward F. McCarthy, MD; Diada R. McCray, ScB; John D. Bacher, DVM; Kevin M. Barnes, PhD; Jeffrey Baron, MD
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Investigation performed at the Unit of Growth and Development, Developmental Endocrinology Branch, National Institutes of Child Health and Human Development, Bethesda, and the Bone Histomorphometry Laboratory and Department of Pathology, The Johns Hopkins University, Baltimore, Maryland

Edwin R. Cadet, MD
Department of Orthopaedic Surgery, New York Presbyterian Hospital-Columbia Presbyterian Medical Center, 622 West 168th Street, PH-11, New York, NY 10032. E-mail address: ed_cadet@hotmail.com

Rachel I. Gafni, MD
Kevin M. Barnes, PhD
Jeffrey Baron, MD
National Institutes of Health, 10 Center Drive, Building 10, Room 10N262, MSC 1862, Bethesda, MD 20892-1862

John D. Bacher, DVM
National Institutes of Health, 10 Center Drive, Building 14E, Room 119A, MSC 5580, Bethesda, MD 20892-1862

Edward F. McCarthy, MD
Diada R. McCray, ScB
Department of Pathology, Johns Hopkins Medical Center, The Harry and Jeanette Weinberg Building, 401 North Broadway Street, Room 2242, Baltimore, MD 21231-2410

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from the Howard Hughes Medical Institute National Institutes of Health Research Scholars Program. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

J Bone Joint Surg Am, 2003 Sep 01;85(9):1739-1748
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Background: The purpose of the present study was to determine whether longitudinal growth of the cortex occurs through intramembranous bone formation involving the periosteum or through endochondral bone formation involving the growth plate and to explore the cellular and biochemical mechanisms responsible for this process.

Methods: Cortical bone formation was studied in the metaphyses of growing New Zealand White rabbits by means of (1) oxytetracycline labeling and fluorescence microscopy, (2) computer-assisted histomorphometry, (3) osteoblast culture and [ 3 H]-thymidine incorporation in the presence of periosteum or periosteum-conditioned medium, and (4) surgical insertion of membranes between the periosteum and the underlying spongiosa.

Results: Within the metaphyseal cortex, oxytetracycline labeling produced fluorescent closed curves outlining enlarging trabeculae derived from coalescing endochondral trabecular bone. In this region of coalescing trabeculae close to the periosteum, osteoblast surface was increased compared with trabeculae farther from the periosteum (p < 0.001). The osteoclast surface did not differ. In vitro, osteoblast proliferation was increased in the presence of periosteum (p < 0.001) or periosteum-conditioned medium (p < 0.001). Surgical insertion of permeable or impermeable membranes between the periosteum and the spongiosa did not prevent cortex formation.

Conclusions: These observations demonstrate that metaphyseal cortical bone is formed by coalescence of endochondral trabecular bone. This coalescence is associated with increased osteoblast surface in the peripheral spongiosa. The increased osteoblast surface could be due to inductive effects of periosteum; in the present study, periosteum stimulated osteoblast proliferation in vitro but was not required for metaphyseal cortical bone formation in vivo.

Clinical Relevance: Understanding metaphyseal cortical growth may help to elucidate the pathophysiology of osseous growth disorders in children.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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