Yale Bulletin and Calendar

April 26-May 3, 1999

Volume 27, Number 30

Grant will support multifaceted
research on human skeleton

Yale has received a five-year, $1.98 million grant from the National Institute of Arthritis, Musculoskeletal and Skin Diseases to foster interdisciplinary research on musculoskeletal disorders, including the common age-associated problem of osteoporosis.

The University is one of only two institutions in the nation to be awarded a Core Center Grant. The grant supports the establishment of the Yale Core Center for Musculoskeletal Diseases, which will allow researchers throughout the campus to collaborate on a range of projects related to the musculoskeletal system. Dr. Karl Insogna, associate professor of medicine (endocrinology), is the principal investigator.

The center will focus on using animal models for acquired and inherited musculoskeletal diseases in humans, according to Insogna, an internationally known expert on metabolic bone disorders. In addition to providing a setting for research to take place, the center will increase interactions between the numerous campus scientists already engaged in musculoskeletal studies, and will support new investigations. Mark C. Horowitz, associate professor of orthopaedics, will co-direct the center with Insogna.

"Yale already has a solid and multifaceted research base in musculoskeletal disorders," Insogna says. "The center gives us an opportunity for further collaboration between investigators, and will help coordinate some of the excellent research already being done here. Investigators will also have the benefit of being able to rely on the expertise of colleagues in different areas of research."

Nearly 30 investigators -- in departments ranging from pediatrics to biology -- have already become affiliated with the new center. They are working on projects geared toward furthering an understanding of musculoskeletal diseases at the level of the whole organism as well as at the cellular and molecular levels. The center's three scientific cores, the Physiology Core, Cell Core and Molecular Core, will support these types of comprehensive studies.

The five-year grant will also support four annual awards of $25,000 each for first-time research on musculoskeletal disorders by Yale staff members. Awards will be made through a formal application and review process. The grant will also fund educational programs, such as symposia, and will finance the administration of the new center.

According to Insogna, an interdisciplinary approach to advancing knowledge of the human skeleton is especially important today.

"Osteoporosis, for example, is a global health problem," says the Yale physician, who also directs the Yale Bone Center, a clinical facility for patients with bone disorders. "Our nation's annual health expenditure for osteoporosis is $14-$15 billion. One in two Caucasian women will have an osteoporotic fracture duing her lifetime. There are 300,000 hip fractures annually, up to 20 percent of which lead to death within a year and, among those who survive, many never regain full independence. In addition, it is estimated that nearly 6 million women have osteoporosis now, many of them undiagnosed. As our older population increases, the annual national expenditure for such problems will double or triple unless major advances are made in the next few years."

Furthermore, he notes, inherited bone disorders "cause tremendous suffering for the people who have them." Among these is X-linked hypophosphatemic rickets, the most common form of inherited rickets in the United States. A considerable effort is being made at Yale to better understand these diseases, according to Insogna. Dr. Thomas O. Carpenter, an associate professor of pediatrics (endocrinology), for example, is studying the gene that causes this form of inherited rickets and is also working with pediatric patients who have the disease.

Other studies focus on how to help prevent falls in the elderly, the causes of hip fracture and how facial bones and teeth develop. Insogna is currently doing clinical research related to the role of diet, particularly protein, in the development of osteoporosis, and is also studying the cellular mechanisms of bone loss caused by parathyroid hormone. Horowitz is engaged in research on the role of cytokines in the differentiation and function of osteoblasts, the bone-forming cells.

The Yale Core Center for Musculoskeletal Diseases will foster collaborative research involving scientists from many departments in the School of Medicine, Yale College, and the University-affiliated John B. Pierce Laboratory. Researchers whose work is even peripherally related to the skeleton are also encouraged to make use of the center, according to Insogna.

He notes, for example, that a researcher in genetics studying a gene that has a major role in blood pressure but that also has an impact on bone can use the Center to study that gene in mice to explore its effects on the skeleton. Scientists can then do further work on the gene's role in bone development or bone disorders by studying bone density and cellular changes in these animals. The cost of some of the research investigators undertake at the new Center is underwritten by the grant; other services are offered at a reduced cost to the investigator.

"Our hope is that people interested in the development of the skeleton will use our facilities and services. As we bring together this diverse group of individual investigators, we strengthen our national role in the understanding of musculoskeletal disorders and further our mission of finding treatments to help those who suffer from them."

For further information on the Yale Core Center for Musculoskeletal Disorders and its Pilot Project Program, e-mail Insogna at karl.insogna@yale.edu.

-- By Susan Gonzalez

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