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CHAPTER
29
Growth and Growth Hormone Use in
Ost
eogenesis Imperfe
cta
Emily L. Germain-Lee
1
, Douglas J. DiGirolamo
2
, and Horacio
Plotkin
3
1
Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD, USA,
2
Johns Hopkins University School of Medicine, Baltimore, MD, USA,
3
University of Nebraska Medical
Center, Omaha, NE, USA and Alexion Pharmaceuticals, Cheshire, CT, USA
IMPAIRED LINEAR GROWTH IN
OST
EOGENESIS IMPERFECTA
(OI)
typical of severe OI),
15-17
it is clear that growth can be
impaired even in the absence of these skeletal abnor-
malities. In an anthropometric study of OI, the heights
of 86 patients in all OI types were lower than the
heights of unaffected family members and followed the
distribution of heights within each type, thereby sug-
gesting that collagen defect
per se
may be the source of
the impaired growth.
1
Even though the heights may
be considered to be “normal” in type I OI, children
and adults have generally lower mean height standard
deviation scores (height SDS) than the general popu-
lation with a mean final height SDS of −2.13.
1
Truncal
and arm span Z-scores are also decreased signifi-
cantly in OI. The arm span Z-score correlates with the
height Z-score,
1
thereby implicating an overall deficit
in growth that is independent of the lower extremity
fractures and scoliosis that can be part of this condi-
tion. Of note, also, is that patients with OI type IV grow
very similarly to those with type III during the first ten
years of life with the same extent of fractures and skel-
etal deformities but have only mild to moderate growth
impairments as adults, indicating that other factors are
involved in linear growth in OI.
2
It has been theorized
that the teleological basis for the short stature could be
“self-protective,” especially in severe OI in which there
is markedly reduced stature; i.e., a shorter bone would
not break as easily as one that is longer.
3,8
Speculation
has been made as to whether abnormalities in the tran-
sition from cartilage to bone as is seen in OI could have
a negative impact on growth.
11
Impaired linear growth and short stature are salient
features of severe OI. These features are also typical of
many children with mild to moderate OI. The etiology
of growth retardation in patients with OI is not com-
pletely understood. In general the poor growth in OI
appears to be more notable in patients with qualitative
collagen defects than in those patients with quantitative
defects,
1-9
thereby making the examination of growth
in children with OI the perfect arena for translational
studies for genotype-phenotype correlations. The pat-
terns of growth in OI have been analyzed most exten-
sively in types I, III and IV OI. Children and adults
with type I OI typically have normal stature or only
minimally affected height reductions; those with type
III OI uniformly have severe short stature accompanied
by numerous fractures and extensive bony abnormali-
ties; and those with type IV OI have, in general, mild
to moderate short stature with a variable phenotype in
terms of linear growth and extent of fractures although
always shorter than their genetic target heights.
1,8,10-14
Other types of OI and syndromes resembling OI pres-
ent with various degrees of short stature.
13
Although it
is obvious that in moderate to severe OI the poor lin-
ear growth and short stature are greatly impacted by
the skeletal abnormalities such as lower limb bowing,
scoliosis, vertebral compression, extremity fractures,
and growth plate disintegration (“popcorn epiphyses”
