This page is dedicated to the Osteogenesis Imperfecta (OI) research study, one of 57 studies supported by the Boston Children’s Rare Disease Collaborative (CRDC). For more information about the CRDC, please visit our home page. Established in 2018, the CRDC supports pediatric rare disease research and provides families with genetic diagnoses that enable personalized treatments, including precision medicine and targeted therapies.

The Osteogenesis Imperfecta (OI) research study, established at Boston Children’s in 2021 and led by Dr. Christina Jacobsen, has enrolled more than 70 patients and their families. The study aims to better understand why children fracture repeatedly, identify genetic causes of OI, and provide personalized medicine.

Disease information

Osteogenesis imperfecta (OI), also known as brittle-bone disease, is a genetic and inherited disorder characterized by fragile bones that break easily without a specific cause. OI is caused by a genetic defect affecting the non-mineral part of bone. However, many patients with multiple (three or more) fractures don’t have a genetic diagnosis. Learn more about OI at Boston Children's.

Key outcomes

Key outcomes include new findings of OI in patients who were previously undiagnosed and candidate findings in 10% of patients that are being further researched.

Genes of interest

COL1A1, COL1A2, CRTAP, LEPRE1, IFITM5, BMP1, WNT1, P4HB, SEC24D

Participate in research

Physicians may refer their patients with multiple fractures, idiopathic juvenile osteoporosis, or OI to Dr. Jacobsen. Once study eligibility is confirmed, a research coordinator will reach out to the family to consent and enroll them. Read more about Dr. Jacobsen’s research on Dr. Jacobsen’s research profile.

Patient care

Patients and their families with multiple fractures/OI can be seen by an expert multidisciplinary team in the Bone Health Program at Boston Children’s.

Patient stories

A 14-year-old patient sought help from an orthopedic clinic due to back pain after a car accident. The medical team identified a spinal compression fracture and recommended a brace, which was removed after a successful period of healing. Subsequent participation in this cohort revealed a genetic mutation in a type 1 collagen gene, COL1A2, known to cause Osteogenesis Imperfecta (OI). The patient inherited this condition from her father, who also had a history of childhood fractures but was never diagnosed with OI. Despite not requiring immediate medical intervention post-puberty as long as the patient remains free of fractures, close monitoring by the doctor continues, with plans to refer the patient to an endocrinologist for future care in adulthood. This genetic discovery provided valuable insight for this patient about her bone health and awareness of potential therapy needs later in life. This diagnosis is also important for reproductive counseling considerations in the future given the dominant inheritance pattern of OI that has a 50% chance of passing it on with each pregnancy.

Investigator

Christina Jacobsen, MD, PhD

Divisions

Notable publications by investigators

  1. 4-PBA Treatment Improves Bone Phenotypes in the Aga2 Mouse Model of Osteogenesis Imperfecta.
  2. Combination therapy in the Col1a2(G610C) mouse model of Osteogenesis Imperfecta reveals an additive effect of enhancing LRP5 signaling and inhibiting TGFbeta signaling on trabecular bone but not on cortical bone.
  3. The Outcomes of Nonelongating Intramedullary Fixation of the Lower Extremity for Pediatric Osteogenesis Imperfecta Patients: A Meta-analysis.
  4. Application of anti-Sclerostin therapy in non-osteoporosis disease models.
  5. Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.
  6. Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta.
  7. Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta.
  8. Sclerostin inhibition reverses skeletal fragility in an Lrp5-deficient mouse model of OPPG syndrome.

Disease support organizations

Osteogenesis Imperfecta Foundation

The Osteogenesis Imperfecta Foundation (OI Foundation) is the only voluntary national health organization dedicated to helping people cope with the problems associated with osteogenesis imperfecta (OI). The Foundation’s mission is to improve the quality of life for people affected by OI through research, education, awareness, and mutual support.

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