Barbara

research

in the clinical setting3

Levine

The role of calcium in the prevention and treatment ofdisease is timely and a number ofour collaborative studies are being conducted under the auspices of our Clinical Nutrition Research Unit (CNRU) investigators. The CNRU is a grant that was awarded by the National Institutes of Health to Memorial Sloan-Kettering Cancer Center, New York Hospital-Cornell University Medical Center and The Rockefeller University in 1980. The grant was expanded in 1985 to include the Hospital for Special Surgery and North Shore University Hospital. The purpose of this program, now in its 10th y, is to advance research, improve nutrition education, and translate the knowledge gained from research into improved prevention and treatment programs for patient care. Our collaborative CNRU now involves these five academic institutions, each with its own special resources and areas of expertise. We bring together clinical and basic scientists from a variety of subspecialties who share a common interest in specific aspects of nutrition. AmJClin Nutr l99l;54:l79S-81S. ABSTRACT

KEY WORDS metabolic bone

Clinical

Nutrition

Research

Unit,

both

clinical

and

basic;

upgrading

the training in nutrition for medical students, physicians, and other health professionals; improving the clinical care of patients at our medical centers and in the population in general; and providing information on nutrition (1). This grant, which was approved and funded for another 5 y, was expanded to include the Hospital for Special Surgery and North Shore University Hospital. Seven components are being developed in this collaborative program; research with human subjects and populations; laboratory investigations; research training; shared research facilities and services; education programs for medical students (2), house staff, practicing physicians, and paramedical personnel; nutritional support services; and public-information activities. Am iC/in

Nuir

l991;54:l79S-81S.

lectures,

Printed

and

joint

research

projects,

we encourage

new ideas and share new knowledge among physicians who care for patients and among research scientists who have the special knowledge that can help clinical medicine. We also encourage practicing

physicians

to look

at the vital

role

ofnutrition

in their

patient care. Our interinstitutional program is ideally suited for promoting interchange among scientists of different disciplines, one of the major goals of this conference, and we are already undertaking a wide range of studies on calcium metabolism.

Research

The role ofcalcium in the prevention and treatment of disease is timely and many of our collaborative studies are being conducted under the auspices of our Clinical Nutrition Research Unit (CNRU) investigators. First it is necessary to describe briefly the CNRU, a grant that was awarded by the National Institutes of Health to Memorial Sloan-Kettering Cancer Center, New York Hospital-Cornell University Medical Center and The Rockefeller University in 1980. This grant application was made to form a unified and coherent program in nutrition for the purposes of advancing research,

conferences,

calcium,

disease

Introduction

multidisciplinary

The purpose ofthis program, now in its 10th y, is to advance research, improve nutrition education, and translate the knowledge gained from research into improved prevention and treatment programs for patient care. Our collaborative CNRU involves five academic institutions, each with its own special resources and areas of expertise. We bring together clinical and basic scientists who share a common interest in specific aspects of nutrition. Through our meetings,

in USA. © 1991 American

coordination

The primary goal of the Research Coordinator of the grant is to aid in stimulating interactions among CNRU members and in developing new projects, thereby advancing multidisciplinary research. Sharing information about collaborative projects is useful to nutrition professionals. It encourages professional networking

and

pooling

of resources,

develops

a large

audience

for

the recruitment ofstudy participants, and extends the knowledge base for researchers in various fields. Specifically, my primary goal as Research Coordinator can be divided into the following objectives: 1) Providing guidance to clinicians and scientists for the development of nutrition-related research and educational programs. Many studies on calcium and bone and cancer and hypertension fall into this category. 2) Encouraging investigators in collaborating institutions to use CNRU core laboratories.

3) Identifying research

needs,

From Medicine,

the

gaps thereby

in knowledge forming the

that constitute important basis for developing pilot

Center and the Department of Cancer Center and New York Hospital-Cornell University Medical College, New York. 2 by NIH grant CA-29502 and by grants from the Donner Foundation, the General Foods Fund, and the SR Bechtel, Jr, Foundation. 3Address reprint requests to B Levine, Nutrition Information Center, 515 East 71st Street, S-904, New York, NY 10021. Society

Nutrition

Memorial

for Clinical

Nutrition

Information

Sloan-Kettering

179S

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Nutrition

180S

LEVINE

studies with

to be reviewed the

and initiated

This

interchange

by scientific

conference

and

has

pointing

out

staff

associated

been

very

useful

where

new

information

is

needed.

4) Recruiting clinical

and

research

ofprofessional

investigations interactions

and students. The Nutrition and

for CNRU-sponsored

state-of-the-art

a directory

trition-related

scientists

volunteers

studies.

5) Publishing strengthen

referring

at

among

staffinvolved

participating

researchers,

in nu-

institutions clinicians,

to

educators,

clinicians

Center,

at our

a resource

collaborating

available

institutions,

to all provides

for identifying and analyzing determinants of food selection and nutritional status among both individuals and populations. Guidance is provided to investigators for developing appropriate methods for nutritional assessment, including computerized nutrient analysis of dietary intake and biochemical and anthropometric measures, and for developing nutrition-education programs for patients in clinical research protocols. Questions about intake, sources, utilization, and therapeutic effects ofcalcium are among those most frequently asked by both health professionals and patients.

and core laboratories

studies

The CNRU program provides funds for a limited number of small pilot studies each year, which allow us to test new ideas and their potential for more intensive study. A successful pilot study, conducted over 1 -2 y, becomes the basis for an indepth investigation meriting separate long-term grant support. Thus, through pilot studies we can develop innovative-research-projects studies

rapidly,

productively,

and

economically.

Our

CNRU

faculty selects pilot studies from a wide range of proposals with the assistance ofa panel ofoutside experts from many nutrition fields. Progress of ongoing studies is monitored regularly. The role of calcium in the prevention and treatment of a variety

of chronic

tigators. is that

One

diseases

has been

of the innovative

it provides

“CNRU

core

to assist

research

Currently 1) The

cancer

funds

laboratories”,

on calcium

we have

a major

features

for

research

which

offer

focus

laboratories, nutrition-related

by our collaborating

five CNRU

core

of our

of the CNRU

laboratories

inves-

program designated analyses

a variety

of bone

metabolism

of nutritional

in patients

with

disorders.

We proposed the establishment of a sixth CNRU core 1990: the carcinogenesis and Nutrition Core Laboratory an indepth

series

oftests

in which individual nutrients mulate a diet that will result risk.

This

goal

that

well-equipped

cells and tissues.

can

by clinical

to handle

Calcium

be used

provides

both

a major

lab in will

to study

can best be manipulated in the greatest reduction

will be accomplished

in a laboratory

ways

to forin cancer

and

basic

studies

human

and

animal

focus

for the studies

on carcinogenesis.

Ongoing

studies

on calcium

metabolism

Within the current grant period there have been many significant advances that have been made possible by the award of the CNRU grant. The highlights ofthese advances as they relate to calcium research are summarized here. Under the direction of Lane and Bockman, the CNRU Metabolic Bone Disease Core Laboratory has advanced to the point where it can provide state-of-the-art noninvasive (radiographic) and invasive (histomorphometric, crystallographic, and biochemical) analyses ofbone orders (3). In conjunction

mation

Center,

determinants

these

metabolism with Levine

investigators

ofcalcium

in a wide variety of the Nutrition

are identifying

metabolism

that

of disInfor-

environmental

affect

susceptibility

to

bone disease and are developing strategies to prevent bone loss in subsets of patients, such as those undergoing adjuvant chemotherapy, radiation and, surgery; anticonvulsant-treated patients with seizure disorders; and patients treated with adrenal steroids for lupus, temporal arteritis, and rheumatoid arthritis. In related studies on bone, Redman et al (4) uncovered a profound deficiency in the dietary intake of calcium-rich nutrients in a cohort of healthy cancer survivors and focused their

scientists.

attention

in operation:

patients disease

Metabolism and Oncology Core Laboratory provides a wide range of assays, has developed methods to determine concentrations of the products of metabolism and trace metals in body fluids and tissues, and seeks to learn how best to assess nutrient status in patients with various disorders, particularly cancer. 2) The Biophysics Core Laboratory has been developing and implementing multidisciplinary approaches to nutrition research, including magnetic-resonance imaging (MRI); various scanning procedures; safe, effective, and rational use of radioisotopes; as well as computerized management of data derived from these procedures. 3) The Immunology Core Laboratory provides state-of-theart analyses of the body’s immune system and its relationship with overall nutritional status. Nutritional assessment and immunological responsiveness of cancer patients are its primary goal. 4) The Lipids Core Laboratory identifies the genetic and environmental factors that regulate metabolism of fat and choles-

analyses

and

provide

Information

a facility

Pilot

Many laboratory assays have been developed to assess with greater accuracy those individuals who may be at increased risk for heart disease and stroke. 5) The Metabolic Bone Disease Core Laboratory, the newest of our CNRU core labs, is a comprehensive unit that performs terol.

in stim-

the

on the metabolic

and

nutritional

needs

who are at high risk of losing bone or its treatment. Gertner, a pediatrician

CNRU

Metabolic

Bone

Disease

Core

ofother

cancer

as a result associated

Lab,

of the with

is determining

the mechanism of the increase of circulating serum calcitriol %concentrations and the corresponding increase in calcium absorption that occurs in early pregnancy, findings that should shed light on the relationship between parity and the ultimate development of postmenopausal osteoporosis, as well as on the factors controlling the intestinal absorption of calcium and phosphate. In a preliminary study assessing the potential hazard of administering calcium porosis in patients

supplements who have

stones,

et al are finding

the

form

urinary risk

Weinerman of calcium

calcium

of new

stone

and

to reduce the risk of osteoa history of having had kidney

citrate

results

citrate

excretion,

formation

should

that giving

and

effective

strategies

in

increases

in

suggesting not

increase

this form of treatment. Because large segments have appropriate concerns about osteoporosis, safe

a supplement

in comparable

for its prevention

that

the net

as a result

of

of the population it is essential that be identified.

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ulating

CNRU.

RESEARCH

IN CLINICAL

abolic

bone

disease,

with a compound

and

promising

results

have

been

obtained

derived from the element gallium by Warrell et al (11). Treatment with this compound may prove to be critical for osteoporosis and Paget’s disease, as well as for preventing premature bone loss in patients with cancer. In addition, Lane et al (3) are studying the nutritional status of elderly patients admitted to the hospital with hip fracture, often the first obvious sign of osteoporosis. This study may help us learn how to use nutrition to prevent this debilitating disorder in elderly people, the fastest-growing segment of the population. Because vitamin D is crucial to bone health in people of all ages, our scientists are assessing which nutritional factors help the body manufacture the most effective forms of vitamin D. The

knowledge we gain from these studies should help us learn whether the diet can be manipulated to prevent the development of the

fractures

that

sometimes

may

occur

in cancer patients pathological

who have not experienced serious trauma (so called fractures).

Summary

and

conclusions

Our collaborative CNRU now involves five academic institutions, each with its own special resources and areas of expertise. We bring together clinical and basic scientists from a variety of subspecialties who share a common interest in specific aspects of nutrition. Many studies, which are collaborative and interdisciplinary, are already in progress and are expected to lead to advances

in the

and disease-the of its proceedings.

understanding

goal ofthis

ofcalcium

conference

metabolism

in health

and of the publication

References 1. Halsted CH. The American Society for Clinical Nutrition ademic society. Am J Clin Nutr l989;50:2 15-20. 2. Levine B. Experiences with required and elective didactic

Cornell

University

Medical

94 1-5. 3. Lane JM, McDonnell Evarts M, ed. Surgery

College.

J, Cornell

as an accourses-

Bull NY Acad Med l989;65:

CN, Henley

JH. Osteoporosis.

In:

of the musculoskeletal system. 2nd ed. New York: Churchill Livingston, 1990:177-98. 4. Redman JR, Bajorunas DR, Wong G, et al. Bone mineralization in women following successful treatment of Hodgkin’s disease. Am J Med l988;85:65-72. 5. Weinerman 5, Levine B, Rodman J, Bockman R, Lane J. Pilot study of calcium citrate supplementation in women with a history or renal stones. J Bone Miner Res 1989;4:S382(abstr). 6. Newman M, Halmi KA. The relationship ofbone density to estradiol and cortisol in anorexia nervosa and bulimia nervosa. Psych Res l989;29: 105-12. 7. Newmark H, Upkin M, MaheshWari N. Colonic hyperplasia and hyperproliferation induced by a nutritional StidietWith fourcomponents ofWestern-style diet. J Nail Cancer Inst l99082:491-6. 8. Lipkin M. Application ofintermediate biomarkers to studies of cancer prevention in the gastrointestinal tract. Am J (in Nutr(in Press). 9. Lipkin M, Friedman E, Winawer SJ, Newmark HL. Colonic epithelial cell proliferation in responders and non-responders to supplemental dietary calcium. Cancer Res l989;49:248-54. 10. Telang NT, Narayanan R, Sweterlish L, Bradlow HL, Osborne MP. Molecular, metabolic and cellular determinants of oncogene-induced transformation in mammary epithelial cells Breast Cancer Res Treat 1989;l3: 143. 11. Warrell RP Jr, Bosco B, Weinerman 5, Levine B, Lane J, Bockman RS. Gallium nitrate for treatment of advanced Paget’s disease of bone: effectiveness and dose-response analysis. Ann Intern Med l990;l 13:847-51.

Downloaded from https://academic.oup.com/ajcn/article-abstract/54/1/179S/4690956 by McMaster University Library, Collections - Serials Processing user on 09 February 2019

Decreased bone mass frequently is found in patients with the eating disorders anorexia nervosa and bulimia nervosa (M Newman, KA Halmi, unpublished observations, 1989), and it has generally been attributed to the low serum estrogen concentrations that result. Newman and Halmi (6) now have shown for the first time that in patients with eating disorders, there is a direct relationship between the serum cortisol secretory rate and bone density. Thus, they proposed the novel hypothesis that hypercortisolemia-not diminished estrogen secretion-may be the cause of decreased bone mass and frequent fractures in anorexia nervosa and bulimia nervosa. In their research studies on nutrition and prevention of cancer, Newmark et al (7) developed a so-called stress diet to use in animal models of carcinogenesis; it resembles the typical Westem-style diet in that it is high in fat and phosphate and low in calcium and vitamin D. These scientists demonstrated that the stress diet induces hyperproliferation and hyperplasia in the colonic mucosa ofboth rats and mice. Raising the amount of calcium in the diet while keeping the other factors constant prevented hyperplasia and hyperproliferation completely in mice and partially in rats. Current studies are determining the effects of manipulating the vitamin D, fat, and phosphate contents while keeping dietary calcium fixed, as well as expanding the scope ofthe investigations to include other tissues from the same animals, namely breast, pancreas, and bladder. Indices under investigation that relate to the proliferation and differentiation ofepithelial cells in various organs include measurements of ornithine decarboxylase (8), tyrosine kinase (9), and oncogene expression (10). The significance ofthis imaginative approach to carcinogenesis and nutrition is that it should make it possible for scientists to identify which specific nutrients in the United States diet, alone and in various combinations, can prevent the evolution of more advanced precancerous lesions in cells, and possibly influence the emergence of tumors without exposure to known chemical carcinogens. Our scientists continue to seek imaginative ways to treat met-

18 iS

NUTRITION