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7701: Longitudinal Study of Osteogenesis Imperfecta


Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. It is seen in both genders and all races. OI can range from very severe to very mild. Individuals with the most severe type of OI may die at birth. People with severe OI who survive may have bowed arms and legs, very short stature and be unable to walk. People with the mildest form of OI may only break bones occasionally and have normal height and lifespan. Breaks can occur in any bone, but are most common in the arms and legs. People with OI also often have problems with the spine. The spine problems include compression fractures and scoliosis (a curvature of the spine). DI is characterized by grey or brown teeth that may chip and wear down and break easily. In addition to weak teeth, the teeth in the upper jaw may not match up with the teeth in the lower jaw.

Before the genetic cause of OI was known, OI was classified into four types. Each type was based upon the symptoms and severity of OI. In most people with OI, the cause is a change in one of the genes that makes a protein called type 1 collagen. In the past decade, it was discovered that in about 5% of people with OI it is in another gene. Some doctors now classify OI both on how severe it is as well as which gene is causing OI. When people classify OI this way, there are more than 10 types of OI. The current standard-of-care for severe types of OI involves the use of IV medications (bisphosphonates) and surgery to put rods in bones to strengthen them. These therapies, although often life-saving, are new and very little is known about their long-term effects on bone and other body systems.

The research aims are:

  1. Perform DNA testing and collect natural history data (information that tracks the disease overtime) on all individuals enrolled in this longitudinal study. We will collect natural history data from all enrolled study participants. The genetic cause of the brittle bone disease will be compared with things like severity, various features and response to treatments. We will store blood and urine samples for future research on OI.

  2. We will see how often people with type I OI have vertebral compression fractures of the spine. We will follow people with OI type 1 who make half the normal amount of type I collagen (main protein in tissue that connects bones) over 5 years. We will do x-rays to see how often they get compression fractures of the vertebrae, what happens over time and any risk factors that increase the risk of these compression fractures.

  3. We will follow people with all forms of OI to see how often they develop scoliosis (curvature of the spine). We will see what risk factors are associated with the worsening of scoliosis. We will also look at the effects of scoliosis on lung function, ability to walk and quality of life. Lastly we will look at the effects of various treatments (bracing, surgery, etc.) on scoliosis and lung function.

  4. We will look at dental health in people with OI. We will do exams, questionnaires and x-rays. We will see how often people with OI have problems with teeth alignment. We will look to see if there are things that result in problems with the teeth and the alignment of the teeth. Importantly, we will see how dental health impacts a person’s quality of life.

About this Study

The purpose of this natural history study is to perform a long-term follow-up of a large group of people with osteogenesis imperfecta (OI). We will collect information including:

  • medical history
  • number of broken bones
  • surgeries done
  • medications taken
  • ability to walk
  • pain
  • lung function and breathing
  • hearing
  • bone mineral density

The overall goal is to improve the health and quality of life of people with OI.

There will be a total of 1000 people with OI in this study.

People that agree to be in the study will be asked to do the following at the yearly study visits:

Study Visit Baseline 12 Month 24 Month 36 Month 48 Month
We will ask you many questions to find out about your quality of life.
Birth History and past surgical history          
Current medical history          
Scoliosis evaluation          
Walking ability Questionnaire          
Dental Quality of Life Questionnaire          
Scoliosis and fractures Quality of Life Questionnaires          
Physical development evaluation          
Medications you are using          
You will be evaluated by the study staff as follows:
We will perform a physical exam          
We will perform a dental exam          
We will assess how well your lungs are working          
We will perform a hearing test          
We will measure your ability to walk and get around          
We will assess your strength and if you are able to do certain things for yourself          
We will perform a Walk Test          
We will take the following X-rays:
We will measure your bone density (strength) with a DEXA scan          
We will take an X-ray of your spine          
We will take an X-ray of your hand          
We will take an X-ray of your jaw          
We will collect the following samples from you:
We will collect 1 teaspoon of blood to study your genes          
We may collect skin cells with a biopsy          
We will collect 1 teaspoon of blood and 2 teaspoon of urine for future research on OI.        

Targeted Enrollment

To be able to participate, you must:

Natural History Study:


  • Have had a DNA test or skin collagen test that proves you have OI
  • Your clinical history and x-rays are highly suggestive of OI, but your diagnosis has not been verified by collagen or DNA testing

Vertebral Compression Fractures component:

  • You have a genetic change where your body makes half the normal amount of collagen. These types of genetic changes are called nonsense or frameshift mutations in COL1A1 or COL1A2 genes

Scoliosis in OI component:

  • You are older than 3 years of age

Dental and Craniofacial Abnormalities in OI component:

  • You are older than 3 years of age and agree to a dental exam and to digital photos of teeth and face being taken.

You are not eligible to participate if:

Natural History Study:

  • You cannot return for study visits at least yearly
  • You have a condition other than OI
  • You have OI and a second genetic or syndromic diagnosis

Vertebral Compression Fractures component:

  • You have used a medication such as bisphosphonates, calcitonin, calcitriol, fluoride, etc., in the past year.
  • You have conditions other than OI that affects muscle and/or bone development (examples include cerebral palsy, rickets, etc.)
  • You have nonsense or frame shift mutations in the final coding exons of COL1A1 or COL1A2.

Scoliosis in OI component:

  • You are unable to have spine x-rays taken.

Dental and Craniofacial Abnormalities in OI component:

  • You refuse the dental examination.

How to participate:

We greatly appreciate your interest in this study and in advancing the understanding of Osteogenesis Imperfecta.

In order to participate, you must contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.

Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.