BONE STRUCTURE AND METABOLISM

Ciba Foundation Symposia

General Volumes :

Visceral Circulation - - - - - Mammalian Germ Cells - - - -

Preservation and Transplantation of Normal Tissues - - - - - - -

Hypertension: Humoral and Neurogenic Factors - - - - - - -

LeukaemiaResearch - - - - -

Chemistry and Biology of Pteridines - - Experimental Tuberculosis - - - -

Porphyrin Biosynthesis and Metabolism -

Histamine - - - - - - -

Extrasensory Perception - - - -

Paper Electrophoresis - - - - -

A leaflet giving fuller details of these aolumes, also of the Ciba Foundation Colloquia on Endocrinology and Colloquia

on Ageing, is available f r o m the Publishers.

CIBA FOUNDATION SYMPOSIUM

B O N E STRUCTURE A N D METABOLISM

ON

Editors for the Ciba Foundation

G . E. W. WOLSTENHOLME, O.B.E., M A . , M.B., B.Ch.

and

CECILIA M. O’CONNOR, B.Sc.

With 121 Illustrations

LITTLE, BROWN AND COMPANY BOSTON

THE CIBA FOUNDATION

for the Promotion of International Co-operation in Medical and Chemical Research 41 PORTLAND PLACE, LONDON, \T7.1.

Trustees : THE RIGHT HON. LORD ADRIAN, O.M., F.R.S.

THE RIGHT HON. LORD BEVERIDGE, K.C.B., F.B.A. THE HON. SIR GEORGE LLOYD-JACOB

MR. RAYMOND NEEDHAM, Q.C.

Director, and Secretary to the Executive Council: DR. G. E. W. WOLSTENHOLME, O.B.E.

Assistant to the Director: DR. H . N. H. GENESE

dssistant Secretary : MISS N. BLAND

Librarian : 11 ISS JOAN ETHERINGTON

Editorial Assistants : MISS C. M. O'CONNOR, B.Sc.

MISS E. C. P. MILLAR, A.H.W.C.

ALL RIGHTS RESERVED

This book m a y not be reproduced by any means, in whole or in part, with- out the permission of the Publishers

Published in London by J . & A. Churchill Ltd. 104 Gloucester Place, W.1

First published 1956

Printed in Great Brituin

PREFACE

THE Ciba Foundation, London, is an educational and scientific charity founded by a Trust Deed made in 1947. Its distinguished Trustees, who are wholly responsible for its administration, are The Rt. Non. Lord Adrian, O.M., F.R.S.; The Rt. Hon. Lord Beveridge, K.C.B., F.B.A. ; The Hon. Sir George Lloyd-Jacob, Kt., and Mr. Raymond Needham, Q.C. The financial support is provided by the world-wide chemical and pharmaceutical firm which has its headquarters in Basle, Switzerland.

The Ciba Foundation forms an international centre where workers active in medical and chemical research are encour- aged to meet informally to exchange ideas and information. It was opened by Sir Henry Dale, O.M., F.R.S., in June 1949.

I n the first six years, in addition to many part-day discus- sions, there have been 37 international symposia, each lasting two t o four days, attended by outstanding workers from many countries. Other symposia are planned a t the rate of five or six a year.

Acting on a suggestion, made a few years earlier, by mem- bers of the committee of the British Bone and Tooth Society, the Director found an opportunity to include a symposium on Bone Structure and Metabolism among the small in- ternational conferences which were organized a t the Ciba Foundation in 1955. Information provided by the foimer honorary secretary of the Society, Dr. T. F. Dixon, now Professor of Biochemistry in Baghdad, and by the present honorary secretary, Dr. H. R. Perkins, was of the greatest value to the Director in the arrangements for this meeting. He also received much advice on membership and the scope of the sessions from Dr. C. E. Dent, who later gave the symposium the benefit of his knowledgeable and benevolent chairmanship.

V

vi PREFACE

The informality and intimacy of these meetings have per- mitted discussion of current and incomplete research and stimulated lively speculation and argument. They have also been the occasion for reference to much published and un- published work throughout the world. The proceedings are issued in full, with only the minimum of editing, in order to pass on to a far wider audience the benefits of these meetings. It is hoped that readers will not only gain informat,ion and inspiration from this report, but will also feel that they share in these frank and friendly discussions.

CONTENTS

PAGE

Chairman’s opening remarks C. E.DENT . 1

Structure of bone from the anatomical to the molecular level

by A. ENGSTROM 3

NORDIN, ROGERS, RUTISHAUSER . . 10

Discussion: ARMSTRONG, BELANGER, BLAXTER, DALLEMAGNE, DENT, EXGSTROX, FOLLIS, LACROIX, LISCO, MEYER,

Structure of bone salts by 11. J. DALLEXAGNE and CLAUDINE FABRY . . 14

Discussion: ARMSTRONG, BELANCER, DE BERNARD, BLAXTER, DALLEMAGNE, ENGSTROM, FANCONI, LACROIX, MEYER, NORDIN . . 32

The histological remodelling of adult bone. An auto- radiographic study

by P. LACROIX . . 36 Discussion: AMPRINO, ARMSTRONG, ENGSTROM, FANCONI,

FOLLIS, KODICEK, LACROIX, LISCO, MEYER . . 4 ! 4

Fibrogenesis and the formation of matrix in developing bone

by S. FITTON JACKSON and J. T. RANDALL . . 47 Discussion: AMPRINO, B~LANGER, FOLLIS, LISCO, MEYER,

NEUBERGER, RANDALL . . 63

The mucopolysaccharides of bone by K. MEYER . . 65

NEUBERGER . . 73 Discussion: B~LANGER, DE BERNARD, KODICEK, MEPER,

Autoradiographic studies of the formation of the organic matrix of cartilage, bone and the tissues of teeth

hy L. F. BELANCER . . 75 BScuSSiOn: ARMSTRONG, BELANGER, BLAXTER, DENT,

KODICEK, MEYER, NEUBERGER, RANDALL . 87 vii

viii CONTENTS

Uptake of 36s in the differentiation and growth of cartilage and bone

by R. AMPRINO . Discussion: ARIPRINO, ARMSTRONG, BELANGER, DENT, ESG-

STROM, FOLLIS, KODICEK, MEYER, Nass~x, NEUBERGCR. NORDIN, RANDALL .

I n vitro uptake and exchange of bone citrate by W. D. ARMST~~ONG and L. SINGER

MEYER, NEUBERGER, PERKINS, RANDALL

. Discussion: ARMSTRONG, BLAXTER, DENT, DIXON, FANCON,

The magnesium content of bone in hypomagnesaemic disorders of livestock

by K. L. BLAXTER . Discussion: ARMSTRONG, BELANGER, BLACK, BLAXTER,

DALLERIAGNE, DENT, DIXON, FOLLIS, HOWARD, LACROIX, NICOLAYSEN, h T ~ ~ ~ ~ ~ .

The mechanism of nutrition in bone and how it affects its structure, repair and fate on transplantation

by W. R. HARRIS and A. W. HAM . Discussion: ARRISTRONG, B~LANGER, ENGSTRORI, FOLLIS,

HARRIS, KODICEK, LACROIX, MEYER, NASSIM . Studies on the repair of fractures using 3 2 P

by P. H. CARTIER, B. DE BERNARD and J. LAGRANGE . Discussion: ARMSTRONG, BLAXTER, DALLEMAGNE, DENT,

FOLLIS, HARRIS, HOWARD, LACROIX, NASSIM, NICOLAYSEN, NORDIN, RUTISHAUSER .

Metabolic studies on vitamin D by E. KODICEK .

Discussion: DENT, FANCONI, KODICEK, MEYER, NASSIM, NICOLAYSEX, NORDIN, ROGERS .

The mode of action of vitamin D by R. NICOLAYSEN and N. EEG-LARSEN .

Discussion: DENT, DIXON, FOLLIS, HOWARD, NICOLAYSEN,

Variations in sensitivity to vitamin D: from vitamin D resistant rickets, vitamin D avitaminotic rickets and hypervitaminosis D to idiopathic hypercalcaemia

NORDIN, PERKINS .

by G. FANCONI .

KODICEK, NASSIII . Discussion : BLACK, BLAXTER, DEST. FANCONI, FOLLTS,

PAGE

89

100

103

113

117

131

135

143

148

158

161 .

172

175

185

187

201

COSTENTS ix PAGE

Present knowledge of parathyroid function, with especial emphasis upon its limitations

by J. E. HOWARD . Discussion: BLAXTER, DIXON, EXOSTROM, FOLLIS, HOWARD,

KODICEK, LACROIX, LISCO, NASSIM, NORDIN, VAN SLYKE . The indirect assessment of parathyroid function

by B. E. C. NORDIN and R. FRASER . Discussion: ARMSTRONG, BLAXTER, DENT, DIXON, FANCONI,

FOLLIS, KODICEK, NASSIM, NICOLAYSEN, NORDIN

Vascularity of bone in relation to pathological studies

.

by E. RUTISHAUSER . Discussion: BLACK, ENGSTROM, FANCONI, FOLLIS, LACROIX,

NORDIN, RUTISHAUSER, STANBURY . Some observations on experimental bone disease

bg R. H. FOLLIS, JR. . Discussion: ARMSTRONG, BELANGER, DE BERNARD, BLAXTER,

DIXON, FANCONI, FOLLIS, HOWARD, KOUICEK, MEYER, NICOLA4YSEN, NORDIN, ROGERS .

Osteodysmetamorphosis foetalis by B. ENGFELDT and R. ZETTERSTROAI .

Discussion: ARMSTRONG, BLACK, DENT, FOLLIS, NASSIM,

Bone as a critical organ for the deposition of radioactive materials

NORDIN, PERKINS .

by H. LISCO . Discussion: BLACK, DEKT, LISCO, MEYER, NASSIM, RUTIS-

HAUSER . General Discussion

ARMSTROPU’G, BELANGER, DENT, FANCONI, FOLLIS, HOWARD, KODICEK, LACROIX, LISCO, NASSIM, NORDIN, RUTISHAUSER .

Chairman’s closing remarks C. E. DENT .

206

218

222

232

239

246

249

255

258

266

272

282

284

291

List of those participating in or attending the Symposium on “Bone Structure and Metabolism ”,

12th-14th July, 1955

R. AMPRINO . W. D. ARMSTRONG

L. F. B~LANGER . B. DE BERNARD J. A. BLACK . K. L. BLAXTER . M. J. DALLEXAGNE

C.E.DENT . T. F. DIXON . A. ENGSTRonI . G. FANCONI . R. H. FOLLIS. JR.

W. R. HARRIS . J. E. HOWARD . E. KODICEK . P. LACROIX . H. LISCO .

K. MEYER . J. R. NASSIM . A. NEUBERGER . R. XIC~OLAYSEN . B. E. C. SORDIX

Inst. of Human Anatomy, University of Bari Dept. of Physiological Chemistry, University

of Minnesota Dept. of Histology and Embryology, School

of Medicine, University of Ottawa Faculty of Medicine, Pans ; and Pavia Royal Hospital for Sick Children, Glasgow The Hannah Dairy Research Inst., Kirkhill,

Inst. of Experimental Therapy, University of

University College Hospital Medical School,

Dept. of Biochemistry, Royal Faculty of

Dept. of Physical Cell Research, Karolinska

Children’s Hospital, Zurich Armed Forces Inst. of Pathology, Washington

Depts. of Surgery and Anatomy, University of

Dept. of Medicine, Johns Hopkins Hospital,

Dunn Nutritional Laboratory, University of

Inst. of Anatomy, University of Louvain Division of Biological and Medical Research,

Argonne Sational Laboratory, Lemont, Illinois

Dept. of Medicine, Columbia University, Sew York

St. George’s Hospital, London Dept. of Chemical Pathology, St. Mary’s

Johan Throne Holst’s Nutritional Research

Postgraduate JIedical School of London

Ayrshire

Liege

London

Medicine, Baghdad

Inst., Stockholm

D.C.

Toronto

Baltimore

Cambridge

Hospital, London

Inst., University of Oslo

xi

xii LIST OF PARTICIPANTS H. R.PERKINS . . . Dept. of Biochemistry, Inst. of Orthopaedics,

J.T.RANDUL . . . Dept. of Physics, King’s College, London H. J. ROGERS . . , National Inst. for Medical Research, Mill

E. RUTISHAUSER . . Dept. of Pathology, University of Geneva

Stanmore, Middlesex

Hill, London

D. D. VAN SLYKE . . Brookhaven National Laboratory, Upton, New York

J. STANBUI~Y . . Massachusetts General Hospital, Boston