Evaluation and Intervention for the Effects of Osteogenesis Imperfecta

NCT00001594 | Completed

• 2 other identifiers: 97006497-CH-0064
• Study Type: observational
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

We propose a longitudinal study of the natural history of types III and IV osteogenesis imperfecta for children age birth to 25 years. A consistent objective throughout this study is to obtain a comprehensive assessment of the natural history and progression of the multiple secondary features of osteogenesis imperfecta. In addition to radiographic, bone density, physical rehabilitation and dental manifestations, we will assess the cardiovascular, pulmonary, neurological, and audiology systems. The major objectives of this protocol focus on rehabilitation and physical therapy studies, pulmonary and cardiovascular function, neurological features, audiological studies and genetic and molecular biology aspects of OI. A major objective in this study is to expand the intensive rehabilitation and physical therapy studies of children with types III and IV OI. This objective continues the work that has been done in the Rehabilitation Department of the Clinical Center for the past 20 years on these patients. However, the focus of this objective is changing to include studies of scoliosis and its effect on function, studies of chest proportions and rib deformities, and studies of nonkinetic variables related to motor performance, such as temperament, competence, coping, and resilience in children with OI. The second major objective is the longitudinal study of pulmonary function in children with types III and IV OI. It is well known that cardiopulmonary complications are a major cause of disability and death in adults with OI; the developmental patterns of these complications, and whether susceptible individuals can be identified in childhood, is unknown. The third major objective of these studies of secondary features is to determine the incidence of basilar invagination and develop a monitoring and management plan for this neurological feature. Next, the prevalence, severity, age of onset and genotypic/phenotypic correlation of hearing loss among children with types II and IV OI remains poorly understood; therefore, the study of audiological features is our fourth major objective. The final major objective in this study is the continued study of the genetic and molecular biology aspect of OI. Patients will have skin biopsies for collagen studies at the biochemical and molecular level. Parents will have blood drawn for determination of mosaic status for the mutation that causes their child s OI. These studies will provide further information on genotype/phenotype correlation and other variables in OI genetics. As appropriate, bone chips from emergency or elective surgical procedures on the participants will be used to study osteoblast function in OI.

Conditions

Osteogenesis Imperfecta

Keywords

Natural History; Brittle Bone; Connective Tissue; Osteogenesis Imperfecta

Outcome Measures

Primary Outcomes (1)

• Ambulation, Basilar Invagination, Secondary Effects of OI

  For the younger children, we evaluated bone density, physical function, dental manifestations, and the cardiovascular, pulmonary, and audiologic systems. Visits for children under 5 will be every 4 months. These assessments will continue when the participants turn 5, with the addition of the neurological system. All children ages 5-18 years will be evaluated at the Clinical Center every 6 months. Ages 19- will be seen on an annual basis

  age-based

Study Arms (1)

Children with OI

Children with OI

Eligibility Criteria

• Age: Up to 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children will be recruited from the United States. This recruitment will be accomplished by our contacts with the Osteogenesis Imperfecta Foundation, parent-to-parent communication, and outside referrals from other health care providers

You may qualify if:

• Children will be recruited from the United States. This recruitment will be accomplished by our contacts with the Osteogenesis Imperfecta Foundation, parent-to-parent communication, and outside referrals from other health care providers.
• Children enrolled in this study will be limited to those with Sillence Types III and IV OI, as determined by clinical and genetic criteria.
• Patients age birth to 10 years at enrollment will be considered for this protocol.
• Children who have not had skin biopsy done for collagen analysis at another facility are preferred for participation in this study. However, previous skin biopsy at another facility will not preclude participation in this protocol.

You may not qualify if:

• Children who can be expected to attain at least some degree of ambulatory skill or have high potential for achieving independent locomotion with assistive technology.
• Children who are clinically too severe to benefit from this program are defined by the following criteria:
• The ratio of head circumference age (the age for which the child's head or body size falls at the 50th percentile) to body length age (the age for which the child's length falls at the 50th percentile) is 7:1 or greater;
• Children who are 24 months of age, and who are unable to sit unsupported for 60 seconds and are unable to demonstrate the ability to prop themselves on upper extremities in the prone position;
• Children who have other significant medical problems, especially severe cardiopulmonary problems, which have an impact on their physical development.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Marini JC. Osteogenesis imperfecta: comprehensive management. Adv Pediatr. 1988;35:391-426. No abstract available.

  PMID: 3055864 BACKGROUND

• Marini JC, Bordenick S, Heavner G, Rose S, Hintz R, Rosenfeld R, Chrousos GP. The growth hormone and somatomedin axis in short children with osteogenesis imperfecta. J Clin Endocrinol Metab. 1993 Jan;76(1):251-6. doi: 10.1210/jcem.76.1.8421094.

  PMID: 8421094 BACKGROUND

• Charnas LR, Marini JC. Communicating hydrocephalus, basilar invagination, and other neurologic features in osteogenesis imperfecta. Neurology. 1993 Dec;43(12):2603-8. doi: 10.1212/wnl.43.12.2603.

  PMID: 8255464 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Osteogenesis Imperfecta

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Study Officials

• Joshua J Zimmerberg, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: January 29, 1997
• Last Updated: April 24, 2026

Record last verified: 2025-07-23

Locations

US (1)