Bone Disease Program of Texas
Description and History
The Rolanette and Berdon Lawrence Bone Disease Program of Texas (RBL BDPT) is a collaborative program that includes the Baylor College of Medicine, M.D. Anderson Cancer Center and University of Texas Health Science Center at Houston. It was established by an initial endowment to the Baylor College of Medicine and M.D. Anderson Cancer Center by Rolanette and Charles Berdon Lawrence, Houston philanthropists. The program was established in 2002 by the two academic institutions to focus on osteoporosis and other Metabolic Bone Disease and spread of cancer to the skeleton in patients with cancer. Baylor College of Medicine's mission in this program is to develop strategies for stimulating new bone formation while The University of Texas M.D. Anderson Cancer Center is focused on bone loss in patients with cancer and the development of strategies to prevent spread of cancer (bone metastasis) into bone. In 2014 a separate endowment established by Rolanette and Charles Berdon Lawrence and others made it possible for the University of Texas Health Science Center at Houston to join the program, bringing expertise in cartilage biology, bone biomechanics and cranial-facial bone biology to the program.
Leadership
Robert F Gagel, M.D. was the founding director of the Bone Disease Program of Texas. The current director (2007) of the Bone Disease Program of Texas is Robert F Gagel, M.D. And the Co-director is Brendan H Lee, M.D., Ph.D. Jacqueline Hecht, Ph.D. is the UT Health Co-director. A Program Advisory Committee that includes representation from both Institutions and an external advisor provides overall direction and supervision. A Development Committee has worked to encourage philanthropic support from the community.
Significance
Osteoporosis is a major health problem. Fractures of the spine or vertebral fractures occur commonly in men and women over the age of 60 and hip fracture remains a leading cause of death in elderly individuals. Repair and rehabilitation of hip fractures currently cost 15 billion dollars per year; as the "baby boomers" enter their 70s (2020) this figure is expected to reach 40-60 billion dollars per year unless effective therapies are developed. Although the introduction of several new therapies have reduced the incidence of fracture by as much as 5-10%, low bone mass leading to fractures remains a major health issue. The Surgeon General's report on osteoporosis, issued in 2004, estimates "One out of every two women over 50 will have an osteoporosis-related fracture in their lifetime, with risk of fracture increasing with age. Due primarily to the aging of the population and the previous lack of focus on bone health, the number of hip fractures in the United States could double or even triple by the year 2020."
It is this challenge that the Bone Disease Program of Texas is committed to address. Recent discoveries indicate that it is possible to build new high quality bone in older citizens. This program is committed to the development of strategies to increase bone mass and strength with the goal of preventing the epidemic of fractures expected over the next two decades.
Organization
The Bone Disease Program of Texas is defined by a contractual relationship among Baylor College of Medicine, M.D. Anderson Cancer Center and the University of Texas Health Science Center Houston. The components include basic laboratory programs at the three institutions that include core facilities (bone density, small animal CT facilities, microCT, biomechanical testing and bone histomorphometric facilities) that are available to members of the program from all institutions. In addition, translational and clinical research programs are being developed at each institution. The program has a monthly seminar series that is held the first Friday of each month at M.D. Anderson and monthly interdisciplinary meetings of researchers within the program (The Bone Club). A new monthly program entitled "T-Bone Meeting" that focuses on education and development of research for trainees will begin during the 2016-2017 academic year.
Participants
Program Advisory Board
Robert F Gagel, M.D., Director; Brendan H Lee, M.D., Ph.D., Co-director; Jaqueline Hecht, Ph.D., Co-director; Sue-Hwa Lin, Ph.D., Member of the Board Thomas R Hunt, M.D., Member of Board; Barbara J Stoll, M.D., Member of the Board
Research Activities
The goal of the program is to stimulate advances in basic and clinical aspects of bone and cartilage disorders across the Texas Medical Center. Each component of the program provides unique expertise and resources that are available to all members of the program. For example, the Baylor College of Medicine (Department of Genetics) runs a molecular core (development of mouse models) and microCT core (under the direction of Brendan H Lee), M.D. Anderson manages the bone histology and histomorphometric core (Robert F Gagel) and the UT Health has developed a biomechanics core under the direction of Catherine Ambrose.
Educational Activities
The Bone Club is a monthly dinner meeting run by the BCM component in which members of the program present their ongoing research. The BDPT monthly seminar series is hosted by MDACC and features nationally and internationally recognized speakers on a broad spectrum of bone-related topics. MDACC also hosts a monthly multi-disciplinary case conference that focuses on osteoporosis and rare bone disorders, with an emphasis on bone problems in the context of malignancy. Texas Children's Hospital (BCM) hosts a monthly patient care conference focused on pediatric bone disorders. The T-Bone Conferences is hosted monthly by BCM and provides an opportunity for graduate and postdoctoral trainees to present their research in an interactive environment.
The RBL BDPT holds an annual retreat that consists of three components. The first is a keynote lecture by a distinguished member of the bone community. The second is a competition for three $45,000 one-year Lawrence Awards, made possibly by generous support from Rolanette and Berdon Lawrence. A short research proposal is submitted by applicants (junior faculty or individuals from outside the bone field who develop a research idea focused on bone). These applications are reviewed and scored by the Directors and members of the program advisory committee with the goal of narrowing the field to 6 applicants. Each finalist presents his/her research plan at the retreat. A panel of experts (from outside any of the member institutions) selects the winners of these one-year grants. Each winner is expected to provide a summary of their work at a subsequent meeting of the program following completion of the grant.
Accomplishments
Participants in this program have made a number of important scientific discoveries. Among them are:
1. Identification of the major regulator of osteoblast differentiation and bone formation, RUNX2 (Gerard Karsenty) 2. Identification of the role of fat cells and the hormone leptin in the regulation of bone formation (Patricia Ducy and Gerard Karsenty) 3. Identification of Osterix, an osteoblast transcription factor that is necessary for normal bone formation and mineralization (Benoit de Crombrugghe) 4. Definition of the physiologic role of the hormone calcitonin (Ana Hoff, Gilbert J Cote, Robert F Gagel) 5. Identification of the relationship between intravenous bisphosphonate use and osteonecrosis of the jaw (Ana Hoff and Robert F Gagel) 6. Characterization of the role of TRAF6 in RANK receptor signaling and the development of inhibitors targeting this molecule to inhibit osteoclast-mediated bone resorption (Bryant Darnay) 7. Characterization of the role of CRTAP, a gene responsible for bone collagen modification, and definition of its role in the osteogenesis imperfecta (Roy Morello and Brendan H Lee)