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CHAPTER
28
The Differential Diagnosis of Adult
Ost
eogenesis Imperfe
cta
Alan Burshell and Satish Pasala
Ochsner Clinic Foundation, New Orleans, LA, USA
INTRODUCTION
blue sclera, premature hearing problems, narrow bones,
short stature, increased flexibility and thin skin on the
dorsum of the hands. The areal bone mineral density
was low and in this family lower at the lumbar spine
than the hip.
Similar to most cases of type I OI there was a single
base pair abnormality leading to a stop codon in one
of the two alpha 1 alleles of type I collagen causing a
quantitative defect in type I collagen. This quantitative
defect in type I collagen is thought to lead directly to
the phenotypic findings.
The challenge and the opportunity is to formulate
some simple general concepts, understand the under-
lying complexity and apply these principles to the dif-
ferential diagnosis. The basic foundation of this chapter
is that AOI or type I OI is predominantly a quantitative
deficiency of type I collagen. Type I collagen is the most
abundant protein in the body and a key structural pro-
tein not only for the bone, but also the tendons, liga-
ments and skin. The phenotype includes not just the
bone, but both skin and joint changes.
Thus, this chapter is really about the matrix of differ-
ent tissues. When the bone is the primary manifestation
then the disease is OI or osteoporosis. If hyperflexibility
and easy bruisability are the presenting symptoms then
the disease is ED syndrome.
OI used to be relatively uncomplicated. Basically,
Sillence types I-IV were autosomal dominant diseases
of type I collagen and explained 90% of the cases.
Recently, several different autosomal recessive gene
mutations were discovered associated with severe or
lethal OI. These have furthered our understanding of
normal type I collagen fiber formation and secretion.
Three genes involved in the 3-hydroxylation of proline
986 as well as collagen chaperone protein abnormalities
The differential diagnosis of adult osteogenesis
imperfecta (AOI) is not something that even bone cli-
nicians think about on a routine basis. The diagnosis is
obvious in patients with a previous diagnosis of neo-
natal or childhood OI and/or a strong family history
of childhood fractures. Blue sclera is a helpful hint to
the diagnosis, but tends to become less prominent with
age and is seen in other diseases such as Ehlers-Danlos
(ED) syndrome. Furthermore, adult OI is not just a dis-
ease of the bones and its emphasis to the detriment of
other organ systems, such as the skin and ligaments,
obviate recognition of similarities with other diseases.
It is likely more subtle presentations are undiagnosed.
The Sillence type I OI (mild OI) is discussed in this
chapter and not the more extreme presentations of neo-
nates and childhood.
Since there is no accepted treatment for adult OI
and there is some doubt as to the benefit of bisphos-
phonates, the nihilist approach might be that the dif-
ferential diagnosis is unimportant. If the differential
diagnosis is between AOI and osteoporosis, then a
bisphosphonate might be indicated for osteoporosis,
but not necessarily for AOI. Thus, from the treatment
perspective it is currently clinically important to dif-
ferentiate these disease processes. Medical therapies
developed specifically for AOI are likely to be of ben-
efit to subgroups of osteoporotic patients with similar
bone pathophysiology. In order to develop an appro-
priate differential diagnosis, the first step is to establish
the phenotype and genotype. We have had the oppor-
tunity to care for and study a large Cajun family with
type I OI. The phenotype in this family was variable,
but the major findings included childhood fractures,
