AGING AND BONE QUALITY

NIH GUIDE, Volume 23, Number 13, April 1, 1994



PA NUMBER:  PA-94-052



P.T.





Keywords:



National Institute on Aging

National Institute of Arthritis and Musculoskeletal and Skin Diseases



PURPOSE



The National Institute on Aging (NIA) and National Institute of

Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invite

research applications to elucidate the nature and consequences of

age-related changes in bone quality and the relationship of these

changes to enhanced bone fragility and susceptibility to osteoporotic

fractures.  Factors that contribute to bone quality include

architecture, density and mechanical strength.



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This Program

Announcement (PA), Aging and Bone Quality, addresses the priority

area of osteoporosis.  Potential applicants may obtain a copy of

"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0) or

"Healthy People 2000" (Summary Report:  Stock No. 017-001-00473-1)

through the Superintendent of Documents, Government Printing Office,

Washington, DC 20402-9325 (telephone 202-783-3238).



ELIGIBILITY REQUIREMENTS



Applications may be submitted by foreign and domestic, non-profit and

for-profit organizations, private and public such as colleges,

universities, laboratories, units of state and local governments, and

eligible agencies of the Federal government.  Foreign institutions

are not eligible for First Independent Research Support and

Transition (FIRST) awards (R29).  Applications from minorities and

women are encouraged.



MECHANISM OF SUPPORT



Support for this program will be by the research project grant (R01)

and the FIRST (R29) award.



RESEARCH OBJECTIVES



Background



The progressive loss of bone with age very commonly leads to

osteoporosis, a condition characterized by increased skeletal

fragility and susceptibility to fracture.  Osteoporosis and its

consequences are a significant cause of frailty, morbidity, and even

mortality.  However, while in older individuals reduced bone mass is

important both in contributing to and predicting an enhanced risk of

fracture, low bone mass alone is not a sufficient explanation for

osteoporotic fractures.  This is exemplified by the substantial

overlap in bone density between normal individuals and patients who

sustain hip and other osteoporotic fractures.  A new perspective is

needed that broadens the conceptual basis of skeletal integrity to

include in addition to bone mass, qualitative factors that may impact

on bone strength such as geometry, macro and micro-structural

organization, distribution of material within bone, biochemical

composition, and the burden of unrepaired microdamage.



An NIA Workshop on Aging and Bone Quality, held September 3-4, 1992,

underscored the need to study bone quality and identified promising

new areas of research, which can be found in the workshop Proceedings

in Calcified Tissue International, Supplement 1, (53), 1993.  This PA

reflects the priority areas that were identified at the workshop.



This PA is directed towards:  (1) stimulating research aimed at

elucidating age-related mechanisms that influence the development

and/or course of osteoporosis and (2) developing strategies aimed at

preventing or lessening the burden of osteoporosis-related fractures

in older individuals.  Specifically, this PA seeks applications for

basic and clinical research to identify and evaluate the effects of

age on factors related to bone quality and/or strategies to modify

the impact of these factors on skeletal fragility and increased

fracture susceptibility.  Topics of interest include, but are not

limited to:



o  Age-related changes in architecture, mechanical properties, and

strength of bone



o  Evaluation of changes in bone matrix and mineralization and their

impact on strength and resistance to microdamage



o  Assessment of the consequences of age on the accumulation of

cortical and trabecular microdamage and their relationship to bone

strength and fracture biomechanics



o  Age-related changes in the detection of microdamage and

activation, and initiation of the remodelling and repair processes in

bone



o  Determination of age- and disease-related changes in biochemical,

cellular, and structural factors affecting bone quality



o  Elucidation of the role and function of osteocytes and bone lining

cells in bone metabolism



o  The nature of changes in osteocyte viability and function with age

and the effect of these changes on the structural and mechanical

properties of bone



o  Development of model systems that reflect normal physical and

physiological aspects related to functional loading and responses to

loading in aged bone



o  Development and application of techniques such as

histomorphometry, ultrasound, NMR, and QCT to evaluate changes in

architecture, bone strength and fracture susceptibility



STUDY POPULATIONS



INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN

SUBJECTS



Awards for research involving human subjects must follow the "NIH

Guidelines On the Inclusion of Women and Minorities as Subjects in

Clinical Research."  See the RFA for details.



APPLICATION PROCEDURES



Applications are to be submitted on the application form PHS 398

(rev. 9/91) available at most institutional offices of sponsored

research and from the Office of Grants Information, Division of

Research Grants, National Institutes of Health, 5333 Westbard Avenue,

Room 449, Bethesda, MD 20892, telephone 301-710-0267.  Applications

will be accepted on the standard application receipt dates as

indicated in the application kit.  The program announcement title and

number must be typed on line 2a of the face page.



FIRST (R29) award applications must include at least three sealed

letters of reference attached to the face page of the original

application.  FIRST award applications submitted without the required

number of reference letters will be considered incomplete and will be

returned without review.



The completed original application and five legible copies must be

sent or delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW CONSIDERATIONS



Applications will be assigned on the basis of established PHS

referral guidelines.  Applications will be reviewed for scientific

and technical merit in accordance with the standard NIH peer review

procedures.  Following scientific-technical review, applications

recommended for further consideration will receive a second-level

review by the appropriate national advisory council.



AWARD CRITERIA



Applications will compete for available funds on the basis of

scientific merit, program balance among research areas of the

announcement, and the availability of funds.



INQUIRIES



Written and telephone inquiries concerning this PA are encouraged.

The opportunity to clarify any issues or questions from potential

applicants is welcome.



Direct inquiries regarding programmatic issues to:



Chhanda Dutta, Ph.D.

Geriatrics Program

National Institute on Aging

Gateway Building, Suite 3E327

Bethesda, MD  20892

Telephone:  (301) 496-1033



Joan A. McGowan, Ph.D.

Bone Biology and Bone Diseases Program

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Westwood Building, Room 403

Bethesda, MD  20892

Telephone:  (301) 594-9957



Direct inquiries regarding fiscal matters to:



Joanne Colbert

Grants and Contracts Management Office

National Institute on Aging

Gateway Building, Room 2N212

Bethesda, MD  20892

Telephone:  (301) 496-1472



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic

Assistance No. 93.866.  Awards are made under authorization of the

Public Health Service Act, Title IV, Part A (Public Law 78-410), as

amended by Public Law 99-158, 42 USC 241 and 285) and administered

under PHS grants policies and Federal Regulations 42 CFR Part 52 and

45 CFR Parts 74 and 92.  This program is not subject to the

intergovernmental review requirements of Executive Order 12372 or to

the Health Systems Agency review.  Awards will be administered under

PHS grants policy as stated in the PHS Grants policy statement, DHHS

Publication NO. (OASH) 90-50,000, revised October 1, 1990.



.

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