Growth Hormone Therapy in Osteogenesis Imperfecta

Conditions:Orthopedic, Endocrine
Therapuetic Areas:Endocrinology, Orthopedics / Podiatry
Age Range:3 - 16
Start Date:November 5, 1991
End Date:May 19, 2017

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Studies of Growth Deficiency and Growth Hormone Treatment in Children With Osteogenesis Imperfecta Types III and IV

Growth deficiency is a key feature of severe Osteogenesis Imperfecta (OI) and a frequent
feature of mild to moderate forms of the disease. The reason that children with OI are short
is not fully understood. We do know that details such as the number of fractures suffered or
the type of OI do not fully explain the short stature of OI. Growth patterns have been
defined for children with OI Types I, III, and IV. At about 12 months of age, children with
Types III and IV OI demonstrate a predictable plateau of their linear growth rate. Type IV OI
children begin to resume a normal growth rate at about age four to five years, but they will
not "catch up" to a normal height, as they have "lost" a significant period of growth. The
plateau usually continues for children with Type III OI. The reason for this growth plateau
is unknown. There have been no studies which evaluate the growth of OI children in this age
range. Our previous studies of growth in OI children have begun at age 5 years.

We have studied growth in OI children for the past 10 years. Different medications have been
tried to both stimulate growth and improve bone density. Some children have responded to
growth hormone (their growth rate increased by at least 50%) and some did not. The majority
of children who did respond were Type IV. However, we need to carefully treat and study more
children to try to determine which children will benefit from growth hormone medication.

The Goals of this Study Are:

1. We want to try to find a cause for the growth plateau common in types III and IV OI.
Long-term, our goal is to develop a treatment to eliminate this plateau.

2. We want to see how long and how well OI bone will respond to growth stimulation.

3. We hope to find a "predictor" for who will respond to growth hormone and who will not,
by measuring your child's endocrine and growth hormone function before receiving any
growth hormone treatment.

4. We want to measure the effects of growth stimulation on bone density, and the quality of
OI bone.

5. We want to see if there are long term benefits resulting from this treatment in the form
of final adult height, trunk height, and possibly improved function of the respiratory

Median Subject Age (on p. 1 of webpage): 1-15 years (replaces 0-20)

Growth deficiency is a cardinal feature of severe Osteogenesis Imperfecta (OI) and a frequent
feature of mild to moderate forms of this disease. Despite the prevalence of short stature
among people with OI, few studies have examined treatment options for this feature of OI.
Recombinant human growth hormone (rGH) is a treatment for growth deficiency which we have
investigated. In our initial studies we have found that many OI children are responsive to
rGH especially those with type IV OI. The purpose of this protocol is to examine the effect
of growth hormone treatment on linear growth of children with types III and IV OI and
correlate growth responsiveness with growth hormone-somatomedin axis and histomorphometry
parameters of OI bone.


Patients will be recruited with the goal of including at least 10 each of individuals with
clinical/biochemical criteria of types III and IV OI who are between 3 and 8 years of age.

Height: Individuals with type III OI have severe short stature by definition; individuals
with type IV OI recruited to the study will have height less than the 3rd percentile for
age. All individuals will be required to furnish growth records, especially height and head
circumference, from at least the preceding two years.

Long bone status: Participants must have radiographic evidence that long bone epiphyses
have not yet fused. In addition, 60 degrees or greater angulation of a femur will exclude a
child, pending surgical management or medical clearance.

Spine: Prospective participants will be evaluated for scoliosis and spinal compressions.
Participants with scoliosis greater than 40 degrees will be excluded unless evidence is
presented that the scoliosis has been stable for the prior two years. Participants with
corrective rods in their spine will be excluded.

Neuro status: All patients will be co-enrolled in 97-CH-0064, and will be screened for
Basilar Invagination through that protocol. Children who are initially screened by spiral
CT scan with MRI confirmation and determined to have severe BI will be excluded from
participation in this study. Severe BI is defined by NIH data as distortion of the angle
between the pons and medulla and or compression of posterior fossa contents. We are only
beginning to define the parameters of BI in this population, and we do not know why some
children with BI progress in severity and some do not. Until those questions are answered,
we feel it would not be prudent to stimulate growth in a child we know to have a severe
form of BI at enrollment.

Pulmonary status: All children will be co-enrolled in 97-CH-0064, and will have pulmonary
function testing through that protocol. Tests will be scheduled as required for that
protocol; namely, PFTs every 2 years if normal, every year if abnormal.


Patients who develop scoliosis greater than 40 degrees and/or patients who progress to
severe basilar invagination during the study will be removed from the study. Failure to
comply with the outlined procedures (blood draws, endocrine testing, bone biopsies, and
visit schedule) is also a criterion for withdrawal from the protocol.

Patients who become pregnant.
We found this trial at
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, MD
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