Blood Supply of Springer London Berlin Heidelberg New York Barcelona Budapest Hong Kong Milan Paris Santa Clara Singapore Tokyo Murray Brookes and William J. Revell Blood Supply of Bone Scientific Aspects

With 235 Figures plus 10 Colour Plates

Springer Murray Brookes, DM (Oxon), MA, DLO (ReS) England Professor Emeritus, University of London Academic Department of Orthopaedics, Rayne Institute, St Thomas's Hospital, Lambeth Palace Road, London SEl 7EH, UK William J. Revell, BA, MSc, PhD (Lond) Academic Department of Orthopaedics, Rayne Institute, St Thomas's Hospital, Lambeth Palace Road, London SEl 7EH, UK

Cover illustrations: Front cover: Sagittal microangiograph of a human fetal (Chapter 3, Figure 2). Back cover: Cross-sectional microangiograph of a canine femur (Chapter 9, Figure 14).

ISBN -13 :978-1-4471-1545-8 British Library Cataloguing in Publication Data Brookes, Murray Blood supply of bone: scientific aspects 1. - Blood-vessels I. Title II. Revell, William J. 612.7'5 ISBN -13:978-1-4471-1545-8 Library of Congress Cataloging-in-Publication Data Brookes, Murray. Blood supply of bone: scientific aspects 1 Murray Brookes and William J. Revell. - Rev. and updated ed. p. cm. Includes bibliographical references and index. ISBN -13:978-1-4471-1545-8 e-ISBN-13 :978-1-4471-1543-4 DOl: 10.1007/978-1-4471-1543-4

1. Bones - Blood-vessels. 2. Bones-Growth. 1. Revell, William J., 1946- . II. Title. [DNLM: 1. Bone and Bones - blood supply. WE 200 B872b 1998) QP88.2.B76 1998 612.7'5 - dc21 DNLMIDLC 97-31214 for Library of Congress CIP Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publi• cation may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of repro graphic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers. © Springer-Verlag London Limited 1998 Softcover reprint of the hardcover 1st edition 1998

This is a revised and updated edition of The Blood Supply ofBone, previously published in 1971 by Butterworth Scientific Ltd. The use of registered names, trademarks etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typeset by EXPO Holdings, Malaysia

28/3830-543210 Printed on acid-free paper Dedication

To Our Wives and Children

Werkleute sind wir, Knappen, Junger, Meister, Und bauen dich, du hohen Mittelschiff.

Das Stundenbuch. Rainer Maria Rilke. Preface to the first edition

This book on the blood supply of bone was begun 5 years ago as an introduction to the anatomical study of the vascular architecture of the skeleton. But the central position held by bone vascularization in the growth and mutability of bones and joints fortunately made the book outgrow its original intention: it has not outgrown its limita• tions. A detailed account of the mechanisms of calcification, col• lagenogenesis and matrix formation has been put aside. Instead I have chosen to emphasize the controlling role of the osseous circula• tion in osteogenesis, and the linkage it provides between bone metab• olism, bone mechanics and bone pathology. In the precious hours that I could sequestrate for my researches from a busy teaching curriculum, I have enjoyed the co-operation of many clinicians and academic colleagues. I would like to acknowledge their kindness in making clinical material or scientific equipment accessible to me, and their timely advice and early encouragement. My thanks are due to the Sir Halley Stewart Trust, the Medical Research Council and the Governors of Guy's Hospital Medical School, who have supported my researches financially. It is particu• larly pleasing for me to record an additional debt that lowe to Professor Roger Warwick, which cannot be repaid by the publication of this book in whose compilation he has shown a continual interest. Among the many who have diligently rendered me technical assis• tance, none will begrudge my mentioning a special debt of gratitude to my wife, for her part-time labour as a research secretary in the midst of a large and lively household.

Murray Brookes 1971

vii Preface to the second edition

More than a quarter of a century has gone by since the publication of the Blood Supply of Bone in 1971. In this time it has been pleasing to see the intensification of bone mechanical and molecular biological studies, if only because the stated aim in the Preface to the first edition was to emphasize the "vascular linkage between bone metab• olism, bone mechanics and bone pathology". That purpose has not changed, and the participation of bone mechanics in the life of bone has never been far from our discussion of the blood supply of bone, the two indivisible aspects of the osteogenic coin. Mechanics affect bone formation; without blood flow there is no osteogenesis. Unfortunately, our subject itself has outgrown its original capacity to include, in a single volume, significant areas of orthopaedic prac• tice. It has therefore become imperative to reserve a subsequent volume devoted to the vascular control of bone remodelling, and its influence on some of the major features of clinical orthopaedics, such as fracture repair, chronic disorders of bone production, bone pros• thetics and skeletal malformation. It is with great pleasure that this book gives us an opportunity to thank Professor Frederick Headey, Head of the Academic Orthopaedic Department in St Thomas's Hospital, London, for always supporting us in our endeavours and providing us, by his own initiat• ives, with space and facilities to carry out bone research for the past 20 years. There can be no question but that without his continual gen• erosity, our collaborative investigations would never have come about, and most certainly this new edition of the Blood Supply of Bone would never have been written. We also thank our postgraduate pupils, who over the years have developed their skills while amplifying our knowledge. We thank, in particular, Mr Richard Brueton, Dr Seba Chandararaj, Mr Mark Churchill, Mr Charles Gallanaugh, Professor Miles Irving, Dr Khin U. May, Mr Mohinder Singh, Mr John Spencer and Professor Darrel Wijeratne, whose thesis work on the skeleton was personally super• vised by one of us (M.B.), and who permitted us to make citation of their research. And most happily we wish to thank Esther Brookes for her daily labour in preparing an acceptable text, including the Bibliography, for our publishers Springer Verlag.

Murray Brookes William Revell 1997

ix Contents

Colour Plates ...... xvii I 1 Iqtroduction ...... 1 ~istorical beginnings ...... 1 Modern vascular studies ...... 3

2 Nutrient vessels in long bones ...... 7 Nutrient ...... 7 Nutrient ...... 7 Arteries of the diaphysis ...... 7 Femoral diaphyseal nutrients ...... 11 Epiphyseo-metaphyseal arteries ...... 13 Diaphyseal nutrient ligation ...... 15 Blood supply oflong bone epiphyses ...... 21 Blood supply of metaphyses ...... 21

3 Modes of bone growth: disposition of the nutrient .. 23 Inequality oflongitudinal bone growth ...... 23 Differential growth at the epiphyses ...... 24 Fetal bone elongation...... 25 Interstitial growth of the periosteum...... 25 Muscle traction on the periosteum ...... 27 Bone remodelling ...... 28 Interstitial growth of systemic vessels ...... 29 Variant systemic arterial pattern ...... 31 Temporal variability of growth patterns...... 32 Conclusion...... 34

4 Early development of nutrient vessels ...... 35 Diaphyseal vessels ...... 35 Epiphyseal vessels...... 42 Formation of the metaphysis ...... 42

5 Blood supply ofirregular bones - 1: Vertebral column. . . . . 46 Vertebral development ...... 46 Vessels of the vertebral column and spinal cord ...... 48 Blood supply of the neural process ...... 49 Arteries ofthe vertebral body ...... 51 Intervertebral joints ...... 52 The vertebral column as a whole ...... 53

xi xii Contents

Blood vessels of the spinal cord ...... 53 Vertebral venous plexuses...... 54

6 Blood supply of irregular bones - 2: Carpal and tarsal bones...... 58 Vessels of the carpus ...... 59 Vessels of individual carpal bones ...... -:~ ...... 60 Hamate...... 60 Capitate ...... 60 Pisiform...... 61 Triquetrum ...... 61 Lunate...... 61 Carpal scaphoid ...... 61 Radio-ulnar articular disc...... 62

7 Blood supply of flat bones...... 64 Bones of the skull ...... 64 Membrane bones ...... 64 Meningeal arteries ...... 69 Flat bones developing in cartilage ...... 70 Pectoral girdle ...... 70 Vessels of the scapula...... 71 Pelvic girdle ...... 71 Vessels of the hip bone ...... 72 Acetabulum ...... 72 Vessels of the ribs ...... 73

8 Blood vessels in ...... 75 Methods ofinvestigation ...... 75 General features of the osseous circulation ...... 78 Vascular patterns ...... 89 Diaphysis ...... 89 Metaphysis ...... 94 Epiphysis ...... 95 Sinusoids in bone marrow...... 96 Pulsation ...... 96 Lobulation and vascular shunts ...... 97 Open and closed circulation ...... 98 Phagocytosis ...... 99 Marrowendothelium ...... 99 Origin of angioblasts ...... 102 Regulators and mediators ...... 103 Conjunction of vascular territories in bone marrow ...... 105

9 Cortex and periosteum ...... 108 Bone structure ...... 108 Blood vessels in the diaphysis...... 108 Young cortex: medullary supply...... 110 Centrifugal flow in young bone cortex ...... 112 Biomechanics of the osseous circulation ...... 115 Contents xiii

Evidencefor blood supply to young bone ...... 116 Concept of a dual blood supply...... 117 Old cortex: medullary and periosteal supply ...... 118 Blood flow in old bone...... 120 Clinical considerations ...... 124 Cortical vascular patterns ...... 125 Pattern determinants in bone cortex...... 126 Vascular neogenesis ...... 131 Periosteum...... 134 Bone cells and endothelial cells ...... 135 Syncytial character of osteocytes ...... 135 Origin of bone cells ...... 136 Factors acting on blood flow in cortex ...... 140

10 Cartilage canals...... 142 Mechanisms of cartilage growth...... 143 Cartilage canal development...... 144 Mechanisms of cartilage canal development...... 145 Nutrient function ...... 147 Epiphysealossification ...... 147

11 Growth cartilages ...... 152 Perichondral vessels...... 153 Metaphyseal subchondral vessels ...... 154 Arterial supply ...... 154 The sinusoid network...... 155 Isogenic columns or clumps ...... 155 Open or closed subchondral sinusoids ...... 157 Vascular and chondrolytic cells ...... 159 Vascular and trabecular pattern...... 165 Mechanism of bone elongation ...... 167 Vessels crossing the cartilage ...... 173 Epiphyseal subchondral vessels ...... 173 Blood supply of growth cartilages ...... 175

12 Synovial joints -1...... 177 Terms of reference ...... 177 Vascular anatomy...... 177 Epiphyseal vessels...... 177 Articular vessels ...... 178 Development of synovial joints ...... 180

13 Synovial joints - 2 ...... 182 Nutrition of articular cartilage ...... 182 Synovial nutrition of joint cartilage...... 182 Synovial membrane ...... 183 Synovial vessels...... 183 Turnover of synovial fluid...... 184 Composition of synovial fluid ...... 185 Synovial cells and hyaluronate...... 186 xiv Contents

Synovial absorptive function ...... 187 Fluid production by capsular synovium ...... 188 Fluid production by transitional synovium ...... 189

14 Synovial joints - 3 ...... 192 Joint lubrication and cartilage nutrition...... 192 Theories oflubrication ...... 192 Load and nutrition ...... 194 Articular nutrition of joint cartilage ...... 194 Permeability of articular bone plate ...... 194 Sulphate and oxygen diffusion...... 196 Centrifugal diffusion from articular plexus...... 197 Cartilage permeability, vascular contact and blood flow. ... 197 Changes in cartilage thickness...... 198 Conclusions...... 199

15 Introduction to bone haemodynamics ...... 203 Low or high pressure system? ...... 203 Regulation of intravascular pressure...... 206 Physical factors influencing flow rates ...... 207 Sinusoid dilatation and hyperaemia ...... 208

16 Measurement of bone vascularity ...... 210 The volume of blood in bone ...... 210 Perfusion methods...... 210 Red cell volume in bone...... 211 Measurement of the vascular mesh ...... 215

17 Bone blood flow measurement -1: Indicator dilution...... 217 Introduction ...... 217 Direct methods...... 217 Venous effluent collection...... 218 Venous plethysmography...... 218 Red cell velocity ...... 219 Pressure, heat and electromagnetism ...... 220 Laser Doppler flowmetry...... 221 Intravascular tracer dilution...... 221 Iodoantipyrene washout ...... 222 Hydrogen washout ...... 223 Red cell dilution and follow-through curves ...... 226 Haematocrit and red cell velocity ...... 230 Flow rate and driving pressure ...... 232 Vascular stress in bone ...... 233 Flow rate and bone formation ...... 233 Plasma shift and synovial water ...... 234

18 Bone blood flow measurement - 2: Clearance of bone seeking tracers ...... 237 Mathematical modelling ...... 242 Dynamic uptake ...... 244 Contents xv

19 Bone blood flow measurement - 3: Arteriolar blockade .... 248 Mixing of tracer particles ...... 249 Site of injection ...... 250 Size and density ...... 251 Arteriolar blockade: nature of particle tracer ...... 252 Resin particles versus microspheres: a practical digression. .. 253

20 Disturbed osseous circulation - 1: Arterial ischaemia...... 266 Fracture repair ...... 266 Arterial ischaemia...... 267 The nutrient artery ...... 267 Metaphyseal arteries ...... 275 Epiphyseal arteries ...... 275

21 Disturbed osseous circulation - 2: Effects of venous obstruction on bone...... 277 Clinical experiences ...... 277 Effects of venous impediment on bone growth ...... 279 Effects of venous impediment on fracture repair ...... 280 Effects of venous impediment on knee joint morphology . .. 282 Venous impediment and clinical osteoarthrosis ...... 283

22 Bone haemodynamics in venous impediment...... 286 Mechanisms of action of venous ligation ...... 291 Haemodynamic changes ...... 291 Intravascular pressure ...... 295 Pressure transduction ...... 296 Stress-generated streaming potentials ...... 296 Hydrostatic pressure ...... 297

23 Vascular control of osteogenesis ...... 299 Mechanical influences on bone formation ...... 299 Strain generated streaming potentials...... 300 Pressure hypothesis ...... 300 Vascular control of osteogenesis ...... 301 Envoi ...... 302

Bibliography ...... 304

Author Index...... 335

Subject Index...... 347 COLOUR PLATES

Fig. 2.14. (far left) Two femoral nutrient foram• ina of similar size on the linea aspera. (Original: Natural size).

Fig. 2.15. (left) Two femoral nutrient for• amina; the upper one is smaller. (Original: Natural size).

posterior median longitudinal - ;";""'- "",-J-~ - _ . ./ posterior spinal arteries

Fig. 5.7. (above) Plan of the spinal cord and its intrinsic blood vessels, united by longitudinal arterial and venous columns. (Based on Gray 1989.) ------.. pevvc Fig. 5.8. (left) Plan of the three great venous circles around each vertebra and the spinal cord, showing pevvc and pivvc, .. _...... - veins of spinal cord external and internal vertebral venous columns; aevvc and aivvc, corresponding anterior columns; and the innermost ~i"'::::=::8::::;;;"",o... _...... _ aivvc venous circles of the spinal cord and .-"------JL-1P-'=-'--'-.::::;~- - .. . basivertebral veins their longitudinal anastomoses. The caval, .... _.... vertebral body azygos, abdominal and pelvic venous systems communicate with the vertebral ~=4j:::==:::4jii=~-- -.... aevvc veins.

xvii xviii Colour Plates

Fig. 8.20. A large nerve bundle dividing at the bifurcation of a medullary artery. (Dog; Linder's silver impregnation; Original magnification X450)

Fig. 8.21. Perivascular fibres in contact with a small epiphyseal artery. (Dog, Linder's silver impregnation; Original magnification X420) Colour Plates xix

Fig. 8.22. Straight in bone marrow with its sympathetic fibres. (Dog, Linder's silver impregnation; Original magnification x420)

Fig. 8.23. A solitary nerve fibre running between parenchymal cells. (Dog, Linder's silver impregnation; Original magnification x420) xx Colour PLates

Fig. 8.38. Photomicrograph of a section through the site of a rat fibular fracture (4 days post• operation), stained with Elbadawi's (1976) hexachrome modification of Movat's stain. The purple "giant cells" close to the blue cartilage, are primitive angioblastic islands in the EM .

Fig. 19.1. Polarized light view of prepared resin particles. The mean length along the long axis is 32.28/-Lm.