Skeletal phenotyping of patients with Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a rare hereditary connective tissue disorder
characterized by increased bone fragility and skeletal deformity. Various
causative genes are known, resulting in a diversity of phenotypic
manifestations and severity of OI. Previous studies on skeletal phenotypes
among different types of OI were mainly limited to measurements of areal bone
mineral density (BMD), whereas bone quality is also determined by bone
microarchitecture. High-resolution peripheral quantitative computed tomography
(HR-pQCT) allows detailed assessment of microarchitecture and strength of the
distal radius and tibia. Currently, the specific microarchitectural properties
of the different OI phenotypes are not well defined and due to the short
stature of patients with some OI-types, it is not known whether the standard
protocol for HR-pQCT imaging is sufficient to assess microarchitecture in OI.

- to compare the skeletal phenotypes of each OI-type obtained at the standard
scan region (i.e. using the fixed offset distance) with a recently published
sex- and site-specific normative dataset of a general adult population,
obtained with the same generation HR-pQCT scanner and at the same region, and
to determine whether deviations from this dataset differ between OI-types
- to compare skeletal phenotypes obtained at the standard scan region with the
genotypes of teh OI-patients with known genotype categorised as a defect COL1A1
or COL1A2
- to explore whether there is a difference in skeletal phenotypes for each
OI-type between the standard scan region and a lenght-dependent scan region.

In this cross-sectional study, patients with known OI, diagnosed and treated at
the Center of Expertise of the Isala Clinic in Zwolle, will visit VieCuri
Medical Center once. During this visit, four HR-pQCT scans will be performed;
two of the distal radius and two of the distal tibia. The first set of scans
(distal radius and distal tibia) will be acquired using the standard HR-pQCT
imaging protocol with a fixed offset distance. The second set of scans (distal
radius and distal tibia) will be acquired with a HR-pQCT imaging with a
relative offset distance depending on the length of the lower arm and leg.
Depending on the mobility of a patient, it is possible that a patient is not
able to position properly and comfortably before the gantry of the scanner, in
which case the scan will not be acquired. All scans will be analysed to
quantify volumetric bone mineral density, cortical and trabecular
microarchitecture, and bone strength.
The bone strength obtained at the standard scan region parameters will be
compared between the different OI-types. For each OI-type separately, bone
strength will also be compared with the recently published normative dataset of
a general adult population, and it will be compared whether deviations from
this dataset differ between the OI-types. Additionally, bone strength will be
compared among genotypes of the OI-patients with a known genotype already
available as part or regular care at the Center of Expertise of the Isala
Clinic in Zwolle. Finally, the bone parameters will be compared between the
standard scan region and the length-dependent scan region, for each OI-type
separately.

Patients do not have any direct benefits from participation in this study, but
participation may provide new insights into the disease that could lead to more
optimal treatment strategies for themselves and other patients with OI. The
risk of study participation is limited to the relatively low radiation
exposure. If a patient*s mobility allows proper and comfortable positioning for
scan acquisition, four HR-pQCT scans of one stack each will be taken: two scans
of the distal radius and two of the distal tibia. Each HR-pQCT scan has an
effective radiation dose of 5 µSv, which brings the total radiation dose of
study participation to 20 µSv (i.e. two radius and two tibia scans). The scans
will be graded according to a clinically used grading system using a five-grade
scale. In case motion artefacts necessitate a repeated HR-pQCT scan, a patient
is exposed to a maximum radiation dose of 40 µSv when all four scans have to be
repeated. This amounts to approximately 0.69% (four scans acquired; no repeated
scans) to 1.38% (four scans acquired and all repeated once) of the average
annual effective background radiation dose per capita in the Netherlands (2.9
mSv). The time to perform the HR-pQCT scans is approximately 2 minutes per
scan, and total visit duration will be approximately 60 minutes.