Genotyping and phenotyping of skeletal deformities in 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.

The primary objective of the study is to identify skeletal phenotypes of adult patients with different OI-types at microarchitectural level with HR-pQCT.
Secondary objectives are:
• to compare the skeletal phenotypes with the genotypes of the OI-types based on clinical symptoms, DXA-based areal bone mineral density and genetic mapping;
• to compare the skeletal phenotypes with sex and site-specific reference data for bone microarchitecture of an adult reference population;
• to explore the preferred site for HR-pQCT scan acquisition (fixed vs. length-dependent offset distance to select scan region).

In this cross-sectional study, approximately 120 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 parameters will be compared with reference data and with type OI (based on clinical symptoms, DXA-based areal bone mineral density, and genetic mapping), which is 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 within the OI-types between the fixed measurement site and relative measurement sites.

this is an observational study identifying skeletal phenotypes of adult patients with different OI-types at microarchitectural level with HR-pQCT.

1 visit at VieCuri medical Center

not applicable