Urinary Biomarkers of OI Pathobiology

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 laboratory testing to
determine OI subtype involves the collection of blood and/or skin cells.

Inclusion Criteria:

- To be able to participate, you must:

Be enrolled in The Longitudinal Study of OI (NTC #02432625) and have one of the following
genetic mutations:

- glycine substitution mutations in COL1A1 or COL1A2

- haploinsufficient mutation in COL1A1 or COL1A2

- mutations in CRTAP, PPIB, or LEPRE1

- mutations in FKBP10 or SERPINH1

- mutations in (SERPINF1, WNT1, or IFITM5)

- dominant negative glycine substitutions and haploinsufficient mutations in COL1A1, and
COL1A2

If you are serving as a control, you must not be related to an individual with OI.

Exclusion Criteria:

- You cannot participate if:

- You are unable to comply with the sample collection schedule.

- You are related to one of the OI subjects and would like to serve as a control
subject.

- You have vertebral instrumentation or spinal deformities where we cannot assess lumbar
spine aBMD.

- You have a history of recent fracture (< 3 months).

- You have serum creatinine above 1x upper limits of normal.

- You have abnormal kidney function.

- You are using Minoxidil.

- You are unable to provide a urine sample readily.