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National Institute of Arthritis and Muscloskeletal and Skin Diseases (NIAMS)

Mild Osteogenesis Imperfecta (OI): Toward Better Understanding and Treatment
April 18 – 19, 2004 Chicago, IL

Agenda Speakers Participants Workshop Summary


Monday, April 19
8:00 a.m. Introduction and Welcome
Peter H. Byers, Michael Whyte, Heller An Shapiro
8:15 a.m. Social context of mild OI
Joan Marini (NIH), Chair
  Membership in the OI Foundation
Heller An Shapiro (OI Foundation)
  Funding for research in mild OI
Joan McGowan (NIAMS)
  The view from inside the family
Leslie Buchbinder-Figa (local parent of child with OI)
  Melanie Pepin (U Washington)
Mild OI and abuse allegations
  Adults with OI in the US health care system
David Rowe (UCONN)
  Mild OI and peer support groups
Deborah Heath (Lewis and Clark)
9:30 a.m. Discussion
10:00 a.m. Clinical aspects of mild OI
Michael Whyte, Chair
  Natural history of mild OI in children
David Sillence (University of Sydney)
  Natural history of mild OI in adults
Jay Shapiro (JHH)
  Onset of hearing loss in mild OI
Finnish Group
  Cardiovascular involvement in mild OI
Richard Wenstrup (Cincinnati)
  Neurological complications in mild OI
Joan Marini (NIH)
  Pregnancy in mild OI
Deborah Krakow
12:00 noon Discussion
1:30 p.m. Molecular basis of mild OI
David Rowe, Chair
  Molecular diagnosis and causes of mild OI
James Hyland (Tulane)
  Splice site mutations in type I collagen genes
Peter Byers
  Linkage studies in non-collagen forms of OI
Frank Rauch (Montreal Shriners)
  The European OI experience
Anne DePaepe (University of Ghent)
  Intracellular events in mild OI
Jeanne Lawrence (U Mass)
3:00 p.m. Discussion
3:30 p.m. Medical and other treatments of mild OI
William G. Cole (Toronto), Chair
  Medical therapies in mild OI, the French trials
Pierre Munier (France)
  Orthopedic management of mild OI in children and adults
William Cole
  Management of hearing loss in mild OI
Finnish Group
  Neurological complication and medical and surgical management
Larry Charnas(University of Minnesota)
  Dental issues and care in mild OI
Scandinavian Group
5:00 p.m. Summary and Discussion
Peter Byers, Michael Whyte, Chairs

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Peter H. Byers, M.D., is a professor of pathology and medicine at the University of Washington, specializing in medical genetics. He also serves as director of the university's Medical Genetics Clinic and Connective Tissue Disease Diagnostic Service. He has published widely on osteogenesis imperfecta as well as other disorders of collagen synthesis, including Ehlers-Danlos and the Marfan syndrome. He recently completed a term as editor of the American Journal of Human Genetics. He earned his M.D. at Case Western Reserve University, completed his residency in internal medicine at the University of California Hospitals in San Francisco, and joined the faculty at the University of Washington in 1977. He is a former chair and current member of the Osteogenesis Imperfecta Foundation's Medical Advisory Council. He served as a board member of the American Society for Human Genetics and as a member and president of the American Board of Medical Genetics. He has received research funding from the Children's Brittle Bone Foundation, and served on the planning committee for the 1999 New Research Strategies in OI Workshop.

Caroline J. Anderson, Ph.D., is a clinical psychologist at Shriners Hospitals for Children, Chicago. In addition to her clinical role, for the past 10 years she has been doing research on the adult outcomes of children with physical disabilities. With her colleague, Dr. Lawrence C. Vogel, Chief of Pediatrics, she is Director of the Transition to Adulthood Program at the hospital. This program includes seminars for adolescents with physical disabilities and their parents. Seminar topics include various aspects of transition, such as healthcare, employment, independent living, and preparing for college. Drs. Anderson and Vogel are also Directors of the Summer Work Program for Teens. This is a grant-sponsored program that provides an opportunity for 12 adolescents with disabilities to be employed by the hospital for 6 weeks during the summer. During that time they also participate in workshops with mentors who discuss transition to adulthood from their own experiences. Dr. Anderson earned her Ph.D. degree from the University of Chicago and began working at Shriners Hospital in 1987.

Lawrence Chamas, M.D., Ph.D., is Assistant Professor of Pediatric Neurology at the University of Minnesota and Program Director for the Child Neurology Residency program. In addition to his active clinical duties, he is interested in genetic disorders that affect the nervous system. His training includes Board Certification in Adult and Child Neurology, Medical Genetics with a subspecialty in Biochemical/Molecular Genetics. Lawrence's current area of research focuses on treatment strategies and outcomes of Hematopoietic Stem Cell Transplantation in Adrenoleukodystrophy. Long term, Lawrence has research interest in the development of novel therapies for genetically controlled neurodegenerative disorders.

Lynn Gerber, M.D., is the chief of the department of rehabilitation medicine at the Warren Grant Magnuson Clinical Center at the National Institutes of Health and also directs the Foot Management Program at the National Rehabilitation Hospital in Washington, D.C. In addition, she is a physician with the arthritis and rheumatism branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) as well as a Clinical Professor at Georgetown University. She has authored or co-authored more than 100 publications, including journal articles and textbook chapters in rehabilitation medicine. She serves as a journal reviewer for the Archives of Physical Medicine and Rehabilitation. Dr. Gerber is a diplomate of the American Board of Internal Medicine, and a diplomate of the American Board of Physical Medicine and Rehabilitation. She completed undergraduate work at Smith College, continuing on to earn her medical degree from Tufts University School of Medicine. She completed internal medicine at the New England Medical Center. A recipient of numerous honors, Dr. Gerber has received WETA's Woman of Achievement, an NIH Director's Award, and a Public Health Service Award for exceptional achievement. Dr. Gerber lectures widely, both nationally and internationally, and has organized national conferences and courses on rehabilitation medicine. She is a member of the OI Foundation's Medical Advisory Council.

Francis Glorieux, O.C., M.D., Ph.D., is the director of research and the founder of the Genetics Unit at the Shriners Hospital for Children in Montreal, Canada. He is also a professor of surgery, pediatrics and human genetics at McGill University. Dr. Glorieux has studied many facets of bone and mineral metabolism and genetic bone disease, including osteogenesis imperfecta. He helped establish a program of molecular diagnosis of collagen defects, and another program to study bones in growing children, helping to define the characteristics of the various forms of OI and defining new types of OI. Since 1992, Dr. Glorieux has been conducting clinical trials to study the effectiveness of pamidronate and alendronate in children with severe OI. Results of these studies have been published in several journals including the New England Journal of Medicine. He chaired the organizing committee for the 7th International Research Conference on OI, held in Montreal in 1999. He is also a member of the OI Foundation's Medical Advisory Council. In 2003, he was the recipient of the Elsevier Award of the International Bone and Mineral Society, and the Jonas Salk Award of the Ontario March of Dimes. Dr Glorieux was recently made an Officer of the Order of Canada, the country's highest honor for lifetime achievement.

James Hyland, M.D., Ph.D., is an Assistant Professor of Pathology at Tulane University Health Sciences Center. Until recently, he was Director of DNA Diagnostics in The Center for Gene Therapy also at Tulane. Dr. Hyland received his Ph.D. in Biology from Temple University. Following post doctoral fellowships at the University of Pennsylvania and a prominent connective tissue laboratory located at Thomas Jefferson University, he entered medical school at the latter institution. His medical education was interrupted for one year when he was a recipient of a Fogarty International fellowship. He continued to study connective tissue disorders during this period at the University of Oulu, Oulu, Finland. He subsequently completed a pathology residency and a hematopathology fellowship also at Thomas Jefferson University Hospital. He is board certified in Clinical Pathology, Anatomical Pathology and Hematopathology.

Kaija Kuurila, M.D., Ph.D., is a specialist in otorhinolaryngology at the Central Hospital of Vaasa, Finland. She has published on hearing loss, balance problems and surgical treatment of hearing loss on osteogenesis imperfecta. She earned her M.D. at Karolinska Institutet in Stockholm, Sweden, completed her residency in otorhinolaryngology at the University of Turku in Finland, and she has worked as a specialist in otorhinolaryngology in Vaasa Central Hospital since 1998. Her thesis "Hearing Loss, Balance Problems and Molecular Defects on Osteogenesis Imperfecta--A Nationwide Study in Finland" was examined and approved at an academic dissertation at Turku University in Finland on December 2003, with Professor David Sillence from University of Sidney, Australia, as an official opponent. She is a member of the Finnish Osteogenesis Imperfecta Foundation's Medical Advisory Council.

Joan Marini, M.D., Ph.D., is chief of the Bone and Extracellular Matrix Branch at the National Institute of Child Health and Human Development. She is a pediatrician, geneticist and molecular biologist. Her current research projects focus on a number of genetic disorders, with a special emphasis on OI. She has served as principal or associate investigator for numerous protocols studying OI, including protocols studying the use of growth hormone therapy and the effects of bracing on ambulation in children with OI. Dr. Marini served on the planning committee for the 1999 New Research Strategies in OI Workshop and chaired the 2001 New Research Strategies in OI Workshop. She is a former chair and current member of the OI Foundation's Medical Advisory Council.

Fergus E. McKiernan, M.D., is the director for the Center for Bone Diseases, Marshfield Clinic, in Marshfield, Wisconsin, where he has a clinical practice in rheumatology and metabolic bone diseases.

Craig Munns, M.B.B.S., Ph.D., F.R.A.C.P., is a Clinical Associate in the Department of Genetics at the Shriners Hospital for Children, Montreal, Canada. He is a pediatric endocrinologist who is undertaking further training in the field of Pediatric Genetic and Metabolic Bone Diseases. At the Shriners, he is involved in the clinical care of children with a wide range of bone disorders including a large cohort with osteogenesis imperfecta. He is involved in research into the effects of bisphosphonates in OI and has written a number of papers in this field. He is also co-editor of the recent publication "Interdisciplinary Treatment Approach for Children with Osteogenesis Imperfecta. He earned his M.B.B.S. and Ph.D. at the University of Queensland, Australia, and did his pediatric and endocrinology training at the Royal Children's Hospital, Brisbane, Australia. His Ph.D. focused on the SHOX gene and its effect on skeletal growth and development. In August 2004 he will commence work as a staff specialist in Genetic and Metabolic Bone Disorders, Department of Endocrinology, The Children's Hospital at Westmead, Sydney, Australia.

Melanie Pepin, M.S., C.G.C., is a board certified genetic counselor and manager of the clinical diagnostic service of the Collagen Diagnostic Laboratory at the University of Washington. Before entering the laboratory and clinical research realm, she provided genetic counseling and support to families of children with inherited disorders, including osteogenesis imperfecta (OI) in the Medical Genetics Clinic at Children's Hospital Medical Center in Seattle. Melanie has published clinical research papers in the areas of prenatal diagnosis of OI, the evaluation of children with unexplained fractures and the Ehlers-Danlos syndromes. She was instrumental in developing the Connective Tissue Special Interest Group of the National Society of Genetic Counselors (NSGC) and been an invited speaker at the national meetings of the American Society of Human Genetics (ASHG) and NSGC on the topic of genetic counseling and OI.

Horacio Plotkin, M.D., is Assistant Professor of Pediatrics and Orthopedic Surgery at University of Nebraska School of Medicine. He is the director of the metabolic bone diseases clinic at Children's Hospital in Omaha, NE, and is PI and co-investigator in several clinical research projects to test the efficacy and safety of bisphosphonates in different bone diseases. Dr. Plotkin has done fellowships on Pediatric Endocrinology (Buenos Aires, Argentina), Metabolic Bone Diseases (Buenos Aires, Argentina), Endocrinology (Yale University, New Haven, CT), and Pediatric Metabolic Bone Diseases (McGill University, Montreal, Canada). He is also the PI of a project to develop computer algorithms and programs for calculation of bone resistance to fracture, using 3D models from 2D images. He has published more than 30 articles related to the field, and is the author of three book chapters.

Cathleen L. Raggio, M.D., is a pediatric orthopaedic surgeon at the Hospital for Special Surgery. She is an assistant professor at Weill-Cornell Medical College and an assistant researcher at the hospital. She has been involved in OI research for the past 6 years both on the basic science level and the clinical level. She has received seed grant funding from the OI Foundation.

David W. Rowe, M.D., is professor of pediatrics at the University of Connecticut Health Center, where he has practiced for 20 years, previously serving as head of the Division of Pediatric Endocrinology/Diabetes. He and his colleagues are currently studying the possibilities for somatic gene therapy for OI. He has published numerous book chapters and journal articles on OI and other inherited disorders of collagen synthesis. He earned his M.D. at the University of Vermont Medical School and, after completing his residency in medicine at Duke University, trained in the collagen research laboratory headed by Dr. George Martin at the National Institute of Dental Research, National Institutes of Health. Several awards and sabbatical leaves allowed him to study DNA cloning, retroviruses, and bone precursor cells. He chairs the OI Foundation's Medical Advisory Council, served on the planning committee for the 1999 New Research Strategies in OI Workshop, and has received research funding from the Children's Brittle Bone Foundation and the OI Foundation.

Heller An Shapiro has worked in nonprofit and volunteer management since 1984. In 1997 she began serving as Executive Director of the Osteogenesis Imperfecta Foundation. Heller An has a Master's Degree in psychology from American University and a BA in psychology from Vassar College. She is a member of the Leadership America class of 1993. Heller An managed volunteers with local organizations such as the DC Hotline and The Kennedy Center, then moved on to chapter/affiliate management in national organizations such as the Foundation Fighting Blindness, VSA arts, and Christmas In April/Rebuilding Together. While serving as Director of Volunteers at the Friends of the Kennedy Center, her program received a 1991 President's Volunteer Action Award. She founded MVP Arts: Managers of Volunteer Programs in the Arts and chaired the 1994 Summit on Trends in Volunteer Leadership Development. In 1997 she worked with Tom Adams to develop and conduct the Executive Development Career Workshop. She served on the board of the Association for Vol- unteer Administration and currently serves on the board of the National Health Council.

Jay Shapiro, M.D., is on the staff of the Kennedy Krieger Institute, Baltimore, MD, as director of the OI Clinic. The goal of the clinic is to develop a multidisciplinary OI program of national scope. Dr. Shapiro also serves as Team Leader, Bone Loss, for the newly created National Space Biomedical Research Institute. From 1990 to 1998 he headed the Clinical Research Center on the Hopkins Bayview Campus. Dr. Shapiro earned his M.D. from Boston University School of Medicine and completed his internal medicine residency at the Albert Einstein College of Medicine. He received his introduction to research in metabolic and inherited bone disorders in the Section on Metabolic Diseases in the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), directed by Dr. G. Donald Whedon. In 1978, Shapiro returned to the NIH Clinical Center, where he eventually became deputy director and then acting director. He has conducted extensive OI research, including studies to identify OI mutations, study the function of mRNA in OI cells, and biochemical studies of the formation of bone matrix by OI skin fibroblasts and bone cells. Current research activities focus on the role of bone marrow stromal cells in bone formation as well as the clinical characteristics and therapy of OI in adults and children. He chaired the Program Committee of the 1994 OI Foundation National Conference, contributed to Managing Osteogenesis Imperfecta: A Medical Manual, and assists OI support groups. He is a member of the OI Foundation's Medical Advisory Council.

Richard J. Wenstrup, M.D., is Professor of Human Genetics and Biomedical Engineering at the University of Cincinnati, Children's Hospital Medical Center. He is also Director of Connective Tissue Clinics and Director of the Molecular Diagnostic Laboratory, Division of Human Genetics at Children's Hospital. Dr. Wenstrup is currently testing the use of ribozymes to inactivate mutant collagen genes, and studying the cellular effects of abnormal collagen deposition in osteoblast cells. He earned his M.D. at the University of Cincinnati Medical School, and has previously served in a number of academic appointments, including Director of the Connective Tissue Diagnostic Facility at the Departments of Medicine and Pediatrics, Duke University. He chairs the OI Foundation Scientific Review Committee and he served on the planning committee for the 1999 New Research Strategies in OI Workshop.

Michael P. Whyte, M.D., developed and is Medical-Scientific Director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospitals for Children in St. Louis. He is also Professor of Medicine, Pediatrics, and Genetics at Washington University School of Medicine, St. Louis and is on staff at Barnes-Jewish Hospital and Children's Hospital, St. Louis. The Research Center serves as a national resource for diagnosis, treatment, and investigation of disorders of bone and mineral metabolism and skeletal dysplasias in children. Whyte and his colleagues currently follow about 150 children with OI. He has authored or coauthored more than 200 scientific papers or book chapters concerning metabolic bone disease. He earned his M.D. at the State University of New York, Brooklyn, and completed his residency in internal medicine at Bellevue Hospital in New York before spending two years as a Clinical Associate at the NIH, followed by a fellowship in endocrinology and then joining the faculty of the Washington University School of Medicine, St. Louis. He is a former chair and current member of the OI Foundation's Medical Advisory Council and served on the planning committee for the 1999 New Research Strategies in OI Workshop.

Priscilla Wacaster, M.D., is a family practice doctor who practices full-time on her family. She and her two children, ages 9 and 3, have Type I OI. After working four years in urgent care, she discovered that with two children with OI, she didn't have time to work! In the past 10 years, the family has experienced 12 surgical procedures and over 35 fractures. In early 1999, the Wacasters began the adventure of travelling the United States in a 40' fifth wheel camper and Freightliner truck. Dr. Wacaster home schools her preschooler and third grader and loves including many great field trips. She serves on the Medical Advisory Council for the OIF and edited the book Managing Osteogenesis Imperfecta: A Medical Manual. She has spoken at OI support group meetings and at the national OI conference in Milwaukee. She is an advocate for early intervention for children with disabilities and for the inclusion of children with disabilities in all aspects of life, including the arts and religious activities.

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David Rowe, M.D. (Chair of the OI Foundation Medical Advisory Council), University of Connecticut Health Center, Department of Genetics and Developmental Biology, Farmington, CN

Lawrence Charnas, M.D., Ph.D., University of Minnesota, Minneapolis, MN

Dan Cohn, Ph.D., Cedars-Sinai Medical Center, Los Angeles, CA

William Cole, Ph.D., M.B.B.S., Hospital for Sick Children, Toronto, Canada

Anne DePaepe, MD, University of Ghent, Belgium

Lynn Gerber, M.D., NIH, Bethesda, MD

Francis Glorieux, M.D., Ph.D., Shriners Hospital for Children, Montreal, Quebec, Canada

Deborah Heath, Ph.D., Lewis and Clark College, Portland, OR

Bill Horton, M.D., Director of Research, Shriners Hospital for Children, Portland, OR

James Hyland, Tulane University, New Orleans, LA

Heidi Kalkwarf, Ph.D., Division of Human Genetics, Children's Hospital Medical Center Cincinnati, OH

Deborah Krakow, M.D., Department of Genetics, Cedars-Sinai Medical Center Los Angeles, CA

Jeanne Lawrence, University of Massachusetts, Amherst, MA

Joan Marini, M.D., Ph.D., NIH, Bethesda, MD

Joan McGowan, Ph.D., NIAMS, Bethesda, MD

Pierre Munier, France

Melanie Pepin, University of Washington, Seattle, WA

Darwin Prockop, M.D., Center for Gene Therapy, Tulane University Medical Center, New Orleans, LA

Frank Rauch, MD, Shriners Hospital for Children, Montreal, Canada

Leon Root, M.D., Hospital for Special Surgery, New York, NY

Jay Shapiro, M.D., Kennedy Krieger Institute, Baltimore, MD

David Sillence, MD, Childrens Hospital, Sydney, Australia

Peter Smith, M.D., Shriners Hospital, Chicago, IL

David Vernick, M.D., Lowry Medical Building, Division of Otolaryngology, Boston, MA

Priscilla Wacaster, M.D., Hot Springs, AK

Matthew Warman, M.D., Department of Genetics, Case Western Reserve University, Cleveland, OH

Richard J. Wenstrup, M.D. (OI Foundation Scientific Review Committee Chair), Division of Human Genetics, Children's Hospital Medical Center, Cincinnati, OH

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Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous group of disorders that range in severity from lethal in the perinatal period to extremely mild with either osteopenia/osteoporosis detected by bone densitometry and a small increase in fracture frequency. The majority of research into the molecular bases, the natural history, and treatment of this group of disorders has focused on the severe end of the spectrum. This meeting was organized to assess the state of information concerning the underlying bases, available therapies, and natural history for individuals on the mild end of the OI spectrum. Peter Byers (University of Washington), Michael Whyte (Washington University) and Heller An Shapiro (OI Foundation) organized and chaired the meeting with support from the agencies listed above. The meeting brought together more than 20 basic and clinical scientists, members of several families with mild forms of OI, and members of the supporting foundation for a one-day conference, preceded by an evening gathering.

The social context of mild forms of OI seems different than that for the more severe forms--in a sense, the mild forms may seem "invisible". Mild forms of OI can escape recognition by clinicians and by colleagues but can, nonetheless limit activities due to fractures and other connective tissue involvement (Amy Jackson, Florida Hospital, Orlando). This may isolate affected individuals from colleagues and peers. Although the OI Foundation provides many services to the OI community and provides many informational materials for individuals with mild forms of OI, the perception is that this group is not well integrated into the biannual meetings (Heller An Shapiro). One significant concern that crosses the medical and social boundaries for families with OI is the risk of being drawn in the Child Protective Services web upon presentation of a young infant with fractures in the ER (Melanie Pepin, University of Washington). Available testing offers solace in some situations but may not affect return to the home. Probably as much as that for the individuals with more severe forms of OI, the transition from integrated care in the pediatric context to "disintegrated" care in the adult context requires active involvement of the caring clinicians, family, and affected family member, and a coordinated transition effort (Caroline Anderson, Shriners Hospital, Chicago).

One issue that crosses the boundaries of diagnosis, testing, and treatment is the clinical criteria that determine the "diagnosis" of OI (Michael Whyte). The issue of whether the diagnosis of "OI" should be limited by mutations in type I collagen genes or should represent a clinical set of findings remains unresolved. When the natural history of people with mutations in type I collagen is examined, considerable variation emerges, as do variations in bone structure (Craig Munns, Shriners Hospital, Montreal). Notable is that individuals with OI type I appear to have small bones with thicker cortex, part of the response to less collagen production. Hearing loss affects about half of individuals with mild forms of OI (Kajia Kuurila, University of Vaasa, Finland) based on studies that define a significant majority of affected individuals in Finland, which also provide the best available data for the prevalence of OI in the population (about 6/100,000). Joint laxity is an issue with many people, but the incidence and prevalence of premature osteoarthritis and other joint related issues is not well documented (Fergus McKiernan, Marshfield Clinic) and skeletal changes, as well as approaches to joint replacement strategies have received less attention than needed (Cathleen Raggio, Weill-Cornell Medical College). Concerns about pregnancy are widespread--will bisphosphonates during childhood limit the ability to mobilize calcium during pregnancy; does pregnancy alter risk of later fracture in people with mild forms of OI; how well defined are risks of pregnancy and how are they related to size? (Priscilla Wacaster, OIF). Finally, neurological complications of OI, including basilar impression, can occur but are rare while other neurological issues could be more common but underappreciated (Lawrence Charnas, University of Minnesota).

The molecular basis of mild forms of OI has been examined extensively but often the complementary studies of mRNA and protein metabolism are missing so that the full picture is left uncertain (James Hyland, Tulane University; Byers).

Treatment of mild forms of OI remains controversial and lessons taken from treatment of elderly women with osteoporosis provide a grounding for non-pharmacological intervention (Whyte). Strength training, attention to the local geography and physical impediments, as well as appropriate footware can all provide stability, fewer falls and fewer fractures. Postural assistance in performance of lifting can have a similar effect (Lynn Gerber, NIH). The use of bisphosphonates, as one choice of drug to inhibit bone resorption, may have effects that are dependent on the maturity of the skeleton (Horacio Plotkin, Children's Hospital, Omaha; Munns, Jay Shapiro, Kennedy-Krieger Institute, Baltimore). Excessive treatment with antiresorptives during growth can interfere with skeletal formation detected by modeling abnormalities and by retention of residual islands of cartilage in newly formed bone. There is concern that this could happen even at the doses currently used (Joan Marini, NIH). The mature skeleton of adults will not, however, provide these clues to toxicity.

The prospect for new gene-based therapies remains and new animals models are coming on-line but more are needed.

This conference raised many more questions than were answered and made it clear that both mild forms of OI and OI in adults were important areas for future research at both the basic and clinical levels.

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Last Reviewed: July 21, 2004
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